Substituted Spiro-Amide Compounds

ABSTRACT

Substituted spiro-amide compounds corresponding to formula I 
     
       
         
         
             
             
         
       
     
     in which R 5  through R 8 , D, X, Y and Z have defined meanings, processes for preparing such spiro-amide compounds, pharmaceutical compositions containing such compounds, and methods of using such spiro-amide compounds for treating and/or inhibiting disorders or disease states mediated at least in part by the bradykinin 1 receptor.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority from U.S. provisional patent application Nos. 61/163,116, filed Mar. 25, 2009, and 61/242,097, filed Sep. 14, 2009. Priority is also claimed based upon European patent application nos. EP 09004235.9, filed Mar. 25, 2009, and EP 09011708.6, filed Sep. 14, 2009.

BACKGROUND OF THE INVENTION

The present invention relates to substituted spiro-amide compounds, processes for the preparation thereof, medicaments containing these compounds and the use of substituted spiro-amide compounds for the preparation of medicaments.

In contrast to the constitutive expression of the bradykinin 2 receptor (B2R), in most tissues the bradykinin 1 receptor (B1R) is not expressed or is expressed only weakly. Nevertheless, expression of B1R can be induced on various cells. For example, in the course of inflammation reactions a rapid and pronounced induction of B1R takes place on neuronal cells, but also various peripheral cells, such as fibroblasts, endothelial cells, granulocytes, macrophages and lymphocytes. In the course of inflammation reactions, a switch from a B2R to a B1R dominance thus occurs on the cells involved. The cytokines interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFα) are involved to a considerable degree in this upwards regulation of B1R (Passos et al. J. Immunol. 2004, 172, 1839-1847). After activation with specific ligands, B1R-expressing cells then themselves can secrete inflammation-promoting cytokines such as IL-6 and IL-8 (Hayashi et al., Eur. Respir. J. 2000, 16, 452-458). This leads to inwards migration of further inflammation cells, e.g. neutrophilic granulocytes (Pesquero et al., PNAS 2000, 97, 8140-8145). The bradykinin B1R system can contribute towards chronification of diseases via these mechanisms. This is demonstrated by a large number of animal studies (overviews in Leeb-Lundberg et al., Pharmacol Rev. 2005, 57, 27-77 und Pesquero et al., Biol. Chem. 2006, 387, 119-126). On humans too, an enhanced expression of B1R, e.g. on enterocytes and macrophages in the affected tissue of patients with inflammatory intestinal diseases (Stadnicki et al., Am. J. Physiol. Gastrointest. Liver Physiol. 2005, 289, G361-366) or on T lymphocytes of patients with multiple sclerosis (Pratet al., Neur-ology. 1999; 53,2087-2092) or an activation of the bradykinin B2R-B1R system in the course of infections with Staphyloccocus aureus (Bengtson et al., Blood 2006, 108, 2055-2063) is found. Infections with Staphyloccocus aureus are responsible for syndromes such as superficial infections of the skin up to septic shock.

Based on the pathophysiological relationships described, there is a great therapeutic potential for the use of B1R antagonists on acute and, in particular, chronically inflammatory diseases. These include diseases of the respiratory tract (bronchial asthma, allergies, COPD/chronic obstructive pulmonary disease, cystic fibrosis etc.), inflammatory intestinal diseases (ulcerative colitis, CD/Crohn's disease etc.), neurological diseases (multiple sclerosis, neurodegeneration etc.), inflammations of the skin (atopic dermatitis, psoriasis, bacterial infections etc.) and mucous membranes (Behcet's disease, pelvitis, prostatitis etc.), rheumatic diseases (rheumatoid arthritis, osteoarthritis etc.), septic shock and reperfusion syndrome (following cardiac infarction, stroke).

The bradykinin (receptor) system is moreover also involved in regulation of angiogenesis (potential as an angiogenesis inhibitor in cancer cases and macular degeneration on the eye), and B1R knockout mice are protected from induction of obesity by a particularly fat-rich diet (Pesquero et al., Biol. Chem. 2006, 387, 119-126). B1R antagonists are therefore also suitable for treatment of obesity.

B1R antagonists are suitable in particular for treatment of pain, in particular inflammation pain and neuropathic pain (Calixto et al., Br. J. Pharmacol 2004, 1-16), and here in particular diabetic neuropathy (Gabra et al., Biol. Chem. 2006, 387, 127-143). They are furthermore suitable for treatment of migraine.

In the development of B1R modulators, however, there is the problem that the human and the rat B1 receptor differ so widely that many compounds which are good B1R modulators on the human receptor have only a poor or no affinity for the rat receptor. This makes pharmacological studies on animals considerably difficult, since many studies are usually conducted on the rat. However, if no activity exists on the rat receptor, neither the action nor side effects can be investigated on the rat. This has already led to transgenic animals with human B1 receptors being produced for pharmacological studies on animals (Hess et al., Biol. Chem. 2006; 387(2):195-201). Working with transgenic animals, however, is more expensive than working with the unmodified animals.

International patent application nos. WO 2008/040492 and WO 2008/046573 describe compounds which, in in vitro assays, show an antagonistic action both on the human B1 receptor and on the B1 receptor of the rat.

International patent application nos. WO 2007/140383 and WO 2007/101007 describe compounds which have an antagonistic action on the macaque B1 receptor in in vitro assays. Experimental data on the activity on the human B1 receptor or the B1 receptor of the rat are not disclosed.

Despite the efforts of the prior art, there continues to be a need for novel B1R modulators, B1R modulators which bind both to the rat receptor and to the human receptor offering particular advantages.

SUMMARY OF THE INVENTION

An object of the present invention was therefore to provide novel compounds which are suitable in particular as pharmacologically active compounds in pharmaceutical compositions.

Another object was to provide novel pharmacologically active compounds which are useful for treating or inhibiting disorders or disease states which are at least partly mediated by B1R receptors.

These and other objects are achieved in accordance with the present invention by providing the substituted spiro-amide compounds described and claimed hereinafter.

The present invention therefore provides substituted spiro-amide compounds corresponding to formula (I)

wherein

-   a represents 0 or 1; -   t represents 1, 2 or 3; -   b represents 0, 1 or 2; -   c, d, e and f each independently represent 0, 1 or 2; -   D represents one of the following groups D1 or D2

-   q represents 0 or 1; -   s represents 0 or 1; -   r represents 1, 2 or 3; -   B represents C(═O), S(═O)₂ or the group —C(═O)—N(R⁹), wherein the     nitrogen atom thereof is bonded to R¹; -   Q₁ and Q₂ each independently represent C, CH or N; -   R¹ represents C₁₋₆-alkyl, aryl, heteroaryl, —CH(aryl)₂,     C₃₋₈-cycloalkyl or an aryl, heteroaryl or C₃₋₈-cycloalkyl bonded via     a C₁₋₆-alkylene group, C₂₋₆-alkenylene group or C₂₋₆-alkynylene     group, or an aryl or heteroaryl group bonded via a C₃₋₆     cycloalkylene group; -   R² represents H, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl, heteroaryl or a     C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₆-alkylene     group; -   R³ and R⁴ together with the group -Q₁-Q₂- joining them form a ring,     which may be unsubstituted or substituted on one or more, for     example 1, 2 or 3, of its carbon ring members by one or more, for     example 1, 2, 3 or 4, substituents independently selected from the     group consisting of F, Cl, Br, I, CF₃, C₁₋₆-alkyl, O—C₁₋₆-alkyl, OH,     OCF₃, SH, SCF₃, aryl and heteroaryl and/or can be fused with at     least one, for example 1 or 2, aryl or heteroaryl, wherein the ring     is saturated, unsaturated one or more times, for example once or     twice, or aromatic, is 4-, 5-, 6- or 7-membered, and can optionally     contain one or more, for example 1, 2 or 3, hetero atoms or hetero     atom groups independently selected from the group consisting of N,     NR⁵⁰, O, S, S(═O) and S(═O)₂; wherein R⁵⁰ denotes H, C₁₋₆-alkyl,     —C(═O)—R⁵¹, C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl,     aryl or heteroaryl group bonded via a C₁₋₃-alkylene group, and R⁵¹     denotes C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl, heteroaryl or a     C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₃-alkylene     group; -   R⁵ represents 0, 1, 2, 3 or 4 substituents independently selected     from the group consisting of F, Cl, CF₃, OCF₃, OH, C₁₋₆-alkyl and     O—C₁₋₆-alkyl and/or two adjacent substituents R⁵ form a fused-on     aryl, heteroaryl or C₄₋₈-cycloalkyl and/or two substituents R⁵     bonded to a carbon atom form a 3, 4 or 5 membered saturated     carbocyclic ring, which may be unsubstituted or substituted on one     or more, for example 1, 2 or 3, of its carbon ring members by one or     more, for example 1, 2, 3 or 4, substituents independently selected     from the group consisting of F, CF₃ and C₁₋₆-alkyl; -   R⁶ represents 0, 1, 2, 3 or 4 substituents independently selected     from the group consisting of F, Cl, Br, CF₃, OCF₃, OH, C₁₋₆-alkyl,     C₃₋₈-cycloalkyl, O—C₁₋₆-alkyl, NO₂, NH₂, N(H)(C₁₋₆-alkyl) and     N(C₁₋₆-alkyl)₂ and/or two adjacent substituents R⁶ form a fused-on     aryl, heteroaryl or C₄₋₈-cycloalkyl; -   R⁷ and R⁸ each independently represent 0, 1, 2, 3 or 4 substituents     which in each case independently of one another are selected from     the group consisting of F, Cl, OH, ═O, C₁₋₆-alkyl, O—C₁₋₆-alkyl,     C₃₋₈-cycloalkyl, aryl, heteroaryl and C₃₋₈-cycloalkyl, aryl or     heteroaryl group bonded via a C₁₋₆-alkylene group and/or two     adjacent substituents R⁷ or R⁸ form a fused-on aryl or heteroaryl; -   R⁹ represents H, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl, heteroaryl or a     C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₃-alkylene     group; -   X represents CR^(10a)R^(10b), NR¹¹ or O; -   Y represents CR^(12a)R^(12b), NR¹³ or O; -   with the proviso that X does not denote NR¹¹ if Y denotes NR¹³; and -   with the proviso that X and Y do not simultaneously denote O; -   wherein -   R^(10a), R^(10b), R^(12a) and R^(12b) independently of one another     each denote H, F, Cl, OH, C₁₋₆-alkyl, O—C₁₋₆-alkyl, C₃₋₈-cycloalkyl,     aryl or heteroaryl, or represent a C₃₋₈-cycloalkyl, aryl or     heteroaryl group bonded via a C₁₋₆-alkylene group, and/or -   in each case R^(10a) and R^(10b) together can represent ═O and/or in     each case R^(12a) and R^(12b) together can represent ═O; -   R¹¹ and R¹³ each independently represent H, C₁₋₆-alkyl,     C₃₋₈-cycloalkyl, aryl or heteroaryl, or denote a C₃₋₈-cycloalkyl,     aryl or heteroaryl group bonded via a C₁₋₆-alkylene group; -   Z represents CR^(14a)R^(14b), NR¹⁵ or O; -   R^(14a) represents H, NR¹⁶R¹⁷, C₁₋₆-alkylene-NR¹⁶R¹⁷,     O—C₁₋₆-alkylene-NR¹⁶R¹⁷, C(═O)—NR¹⁶R¹⁷, C(═O)—C₁₋₆-alkylene-NR¹⁶R¹⁷,     OR¹⁸, C₁₋₆-alkylene-OR¹⁸, C₁₋₆-alkylene-O—C₁₋₆-alkylene-OR¹⁸,     C₁₋₆-alkyl, C₃₋₈-cycloalkyl, heterocyclyl, aryl or heteroaryl, or     denotes a C₃₋₈-cycloalkyl, heterocyclyl, aryl or heteroaryl group     bonded via a C₁₋₆-alkylene group, -   R^(14b) represents H, NR¹⁶R¹⁷, C₁₋₆-alkylene-NR¹⁶R¹⁷,     O—C₁₋₆-alkylene-NR¹⁶R¹⁷, C(═O)—NR¹⁶R¹⁷, C(═O)—C₁₋₆-alkylene-NR¹⁶R¹⁷,     OR¹⁸, C₁₋₆-alkylene-OR¹⁸, C₁₋₆-alkylene-O—C₁₋₆-alkylene-OR¹⁸,     C₁₋₆-alkyl, C₃₋₈-cycloalkyl, heterocyclyl, aryl or heteroaryl, or     denotes a C₃₋₈-cycloalkyl, heterocyclyl, aryl or heteroaryl group     bonded via a C₁₋₆-alkylene group, -   R¹⁵ represents H, —C(═O)—R¹⁹, —S(═O)₂—R¹⁹, —C(═O)—N(R²⁰)—R¹⁹,     CHR²⁵R²⁶, C₁₋₁₀-alkyl, C₃₋₈-cycloalkyl, heterocyclyl, aryl or     heteroaryl or denotes a CHR²⁵R²⁶, C₃₋₈-cycloalkyl, heterocyclyl,     aryl or heteroaryl group bonded via a C₁₋₆-alkylene group; -   R¹⁶ and R¹⁷ each independently represent H, C₁₋₆-alkyl or     C₃₋₈-cycloalkyl, or -   R¹⁶ and R¹⁷ together with the nitrogen atom joining them form a     heterocyclic ring, which may be unsubstituted or substituted on one     or more, for example 1, 2 or 3, of its carbon ring members by one or     more, for example 1, 2, 3 or 4, substituents independently selected     from the group consisting of F, Cl, Br, I, CF₃, C₁₋₆-alkyl,     O—C₁₋₆-alkyl, OH, OCF₃, SH, SCF₃, NR^(A)R^(B), aryl and heteroaryl     and/or can be fused with at least one, for example 1 or 2, aryl or     heteroaryl, wherein the heterocyclic ring is saturated or     unsaturated one or more times, for example once or twice, is 4-, 5-,     6- or 7-membered, and can optionally contain one or more, for     example 1, 2 or 3, hetero atoms or hetero atom groups independently     selected from the group consisting of N, NR^(50a), O, S, S(═O) and     S(═O)₂; wherein R^(50a) denotes H, C₁₋₆-alkyl, —C(═O)—R^(51a),     C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or     heteroaryl group bonded via a C₁₋₃-alkylene group, and R⁵¹ denotes     C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl,     aryl or heteroaryl group bonded via a C₁₋₃-alkylene group; -   R¹⁸ represents H, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, heterocyclyl, aryl,     heteroaryl or C₂₋₆-alkylene-NR¹⁶R¹⁷ or denotes a heterocyclyl,     C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₆-alkylene     group; -   R¹⁹ represents C₁₋₆-alkyl, aryl, heteroaryl, —CH(aryl)₂,     C₃₋₈-cycloalkyl, heterocyclyl or an aryl, heteroaryl,     C₃₋₈-cycloalkyl or heterocyclyl bonded via a C₁₋₆-alkylene group,     C₂₋₆-alkenylene group or C₂₋₆-alkynylene group; -   R²⁰ represents H, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl, heteroaryl or a     C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₃-alkylene     group;     or -   if X represents O and f represents 0, then Z denotes     —(C(R²¹)—C(R²²))—, wherein -   R²¹ and R²², together with the carbon atoms joining them, form a     fused-on aryl or heteroaryl; or -   if X represents O and f represents 0, then Z denotes ═(N(CR²³))—,     wherein the N atom is bonded to the O atom via a single bond, and -   R²³ represents H, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl or heteroaryl or     denotes a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a     C₁₋₆-alkylene group; -   R²⁵ and R²⁶ each independently represent H, C₁₋₄-alkyl,     C₃₋₈-cycloalkyl, aryl or heteroaryl, or -   R²⁵ and R²⁶ together with the CH grouping joining them form a ring,     which may be unsubstituted or substituted on one or more, for     example 1, 2 or 3, of its carbon ring members by one or more, for     example 1, 2, 3 or 4, substituents independently selected from the     group consisting of F, Cl, Br, I, CF₃, C₁₋₆-alkyl, O—C₁₋₆-alkyl, OH,     OCF₃, SH, SCF₃, NR^(A)R^(B), aryl and heteroaryl, wherein the ring     is saturated or unsaturated one or more times, for example once or     twice, but is not aromatic, is 4-, 5-, 6- or 7-membered, and can     optionally contain one or more, for example 1, 2 or 3, hetero atoms     or hetero atom groups independently selected from the group     consisting of N, NR^(50b), O, S, S(═O) and S(═O)₂; wherein R^(50b)     denotes H, C₁₋₆-alkyl, —C(═O)—R^(51b), C₃₋₈-cycloalkyl, aryl,     heteroaryl or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via     a C₁₋₃-alkylene group, and R^(51b) denotes C₁₋₆-alkyl,     C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or     heteroaryl group bonded via a C₁₋₃-alkylene group; -   R^(A) and R^(B) each independently represent H, C₁₋₆-alkyl or     C₃₋₈-cycloalkyl, or -   R^(A) and R^(B) together with the nitrogen atom joining them form a     heterocyclic ring, which may be unsubstituted or substituted on one     or more, for example 1, 2 or 3, of its carbon ring members by one or     more, for example 1, 2, 3 or 4, substituents independently selected     from the group consisting of F, Cl, Br, I, CF₃, C₁₋₆-alkyl,     O—C₁₋₆-alkyl, OH, OCF₃, SH, SCF₃, aryl and heteroaryl, wherein the     heterocyclic ring is saturated or unsaturated one or more times, for     example once or twice, but is not aromatic, is 4-, 5-, 6- or     7-membered, and can optionally contain one or more, for example 1, 2     or 3, hetero atoms or hetero atom groups independently selected from     the group consisting of N, NR^(C), O, S, S(═O) and S(═O)₂; wherein     R^(C) denotes H, C₁₋₆-alkyl, —C(═O)—R^(D), C₃₋₈-cycloalkyl, aryl,     heteroaryl or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via     a C₁₋₃-alkylene group, and R^(D) denotes C₁₋₆-alkyl,     C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or     heteroaryl group bonded via a C₁₋₃-alkylene group; and

wherein the partial structure

is preferably bonded to the base structure in position x or y, and

wherein the abovementioned C₁₋₄-alkyl, C₁₋₆-alkyl, C₁₋₁₀-alkyl, C₁₋₃-alkylene, C₁₋₆-alkylene, C₂₋₆-alkylene, C₂₋₆-alkenylene, C₂₋₆-alkynylene, C₃₋₈-cycloalkyl, C₄₋₈-cycloalkyl, heterocyclyl, aryl and heteroaryl groups can in each case be unsubstituted or substituted one or more times by identical or different substituents and the abovementioned radicals C₁₋₄-alkyl, C₁₋₆-alkyl, C₁₋₁₀-alkyl, C₁₋₃-alkylene, C₁₋₆-alkylene, C₂₋₆-alkylene, C₂₋₆-alkenylene and C₂₋₆-alkynylene can in each case be branched or unbranched;

in the form of the free compounds; of the tautomers; of the N-oxides; of the racemate; of the enantiomers, diastereomers, mixtures of the enantiomers or diastereomers or of an individual enantiomer or diastereomer; or in the form of the salts of physiologically acceptable acids or bases.

In the context of the present invention, the term “halogen” preferably represents F, Cl, Br and I, in particular F and Cl.

In the context of this invention, the expression “C₁₋₁₀-alkyl”, “C₁₋₆-alkyl” or “C₁₋₄-alkyl” includes acyclic saturated hydrocarbon groups having 1-10 C atoms, 1, 2, 3, 4, 5 or 6 C atoms or, respectively, 1, 2, 3 or 4 C atoms, which can be branched- or straight-chain (unbranched) and unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, by identical or different substituents. The alkyl groups can preferably be selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl and hexyl. Particularly preferred alkyl groups are selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl and tert-butyl.

In the context of this invention, the expression “C₃₋₈-cycloalkyl”, “C₄₋₈-cycloalkyl” or “C₃₋₆-cycloalkyl” denotes cyclic saturated hydrocarbons having 3, 4, 5, 6, 7 or 8, having 4, 5, 6, 7 or 8 or, respectively, having 3, 4, 5 or 6 carbon atoms, which can be unsubstituted or substituted once or more times, for example by 2, 3, 4 or 5 identical or different substituents, on one or more ring members. C₃₋₈-Cycloalkyl can preferably be selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

The term “heterocyclyl” includes saturated or unsaturated (but not aromatic) cycloalkyls having three to seven ring members, in which one, two or three carbon atoms are replaced by a hetero atom in each case independently of one another chosen from the group S, N or O, wherein the ring members can be unsubstituted or substituted one or more times. The bonding of the heterocyclyl to the main general structure can be via any desired and possible ring member of the heterocyclyl radical. The heterocyclyl groups can also be condensed with further saturated, (partially) unsaturated or aromatic or heteroaromatic ring systems, which in turn can be unsubstituted or substituted one or more times. Heterocyclyl groups selected from the group consisting of azetidinyl, aziridinyl, azepanyl, dioxanyl, dioxolanyl, morpholinyl, pyranyl, pyrrolidinyl, piperazinyl, piperidinyl, pyrazolidinyl, pyrazolinonyl or thiomorpholinyl are preferred.

Cycloalkyl and heterocyclyl groups also may be bridged by C₁₋₆-alkylene, preferably by C₁₋₃-alkylene, as, for example, in

Where an aryl or heteroaryl group is bonded via a C₃₋₆ cycloalkylene group this bonding may be effected via the same or different carbon atoms of the cycloalkylene group, e.g

In the context of this invention, the expression “aryl” denotes aromatic hydrocarbons, in particular phenyls and naphthyls. The aryl groups can also be condensed with further saturated, (partially) unsaturated or aromatic ring systems. Each aryl group radical can be unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, wherein the substituents on the aryl can be identical or different and can be in any desired and possible position of the aryl. Aryl can advantageously be selected from the group consisting of phenyl, 1-naphthyl and 2-naphthyl, which in each case can be unsubstituted or substituted one or more times, for example by 2, 3, 4 or 5 substituents.

In the context of the present invention, the expression “heteroaryl” represents a 5-, 6- or 7-membered cyclic aromatic group which contains at least 1, optionally also 2, 3, 4 or 5 hetero atoms, wherein the hetero atoms can be identical or different and the heteroaryl can be unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, by identical or different substituents. The substituents can be bonded in any desired and possible position of the heteroaryl. The heterocyclic ring can also be part of a bi- or polycyclic, in particular a mono-, bi- or tricyclic system, which can then be more than 7-membered in total, preferably up 5 to 14-membered. Preferred hetero atoms are independently selected from the group consisting of N, O and S. The heteroaryl group can be selected, for example, from the group consisting of isoxazolyl, [1,2,3]-thiadiazolyl, pyrrolyl, indolyl, furyl (furanyl), benzofuranyl, thienyl (thiophenyl), benzimidazolyl, benzothienyl, benzothiadiazolyl, benzothiazolyl, benzotriazolyl, benzodioxolanyl, benzodioxanyl, benzooxazolyl, benzooxadiazolyl, imidazothiazolyl, dibenzofuranyl, dibenzothienyl, phtalazinyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, oxadiazolyl, triazinyl, triazole, tetrazole, isoxazoyl, pyridinyl (pyridyl), pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl, indazolyl, purinyl, indolizinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenazinyl, phenothiazinyl and oxadiazolyl, in particular from the group consisting of thienyl (thiophenyl), pyridinyl (pyridyl), pyrimidinyl, thiazolyl, triazolyl, imidazolyl, oxazolyl, oxadiazolyl, quinazolinyl, quinolinyl and isoquinolinyl, wherein bonding to the general structure (I) can be via any desired and possible ring member of the heteroaryl radical. The heteroaryl radical can preferably be selected from the group consisting of pyrrolyl, indolyl, furyl (furanyl), benzofuranyl, thienyl (thiophenyl), benzimidazolyl, benzothienyl, benzothiadiazolyl, benzothiazolyl, benzotriazolyl, benzodioxolanyl, benzodioxanyl, benzooxazolyl, benzooxadiazolyl, imidazothiazolyl, dibenzofuranyl, dibenzothienyl, phtalazinyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, oxadiazolyl, triazinyl, triazole, tetrazole, isoxazoyl, pyridinyl (pyridyl), pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl, indazolyl, purinyl, indolizinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenazinyl, phenothiazinyl and oxadiazolyl, in particular from the group consisting of thienyl (thiophenyl), pyridinyl (pyridyl), pyrimidinyl, thiazolyl, triazolyl, imidazolyl, oxazolyl, oxadiazolyl, quinazolinyl, quinolinyl and isoquinolinyl, wherein bonding to the general structure (I) can be via any desired and possible ring member of the heteroaryl group.

The heteroaryl group can particularly preferably be selected from the group consisting of thienyl, imidazoyl, thiazolyl, triazolyl, pyridinyl and pyrimidinyl.

In the context of the present invention, the expression “C₁₋₃-alkylene group”, “C₁₋₆-alkylene group” or “C₂₋₆-alkylene group” includes acyclic saturated hydrocarbon groups having 1, 2 or 3 C atoms, 1, 2, 3, 4, 5 or 6 C atoms or, respectively, 2, 3, 4, 5 or 6 C atoms, which can be branched- or straight-chain (unbranched) and unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, by identical or different substituents and which link a corresponding radical to the main general structure. The alkylene groups can preferably be selected from the group consisting of —CH₂—, —CH₂—CH₂—, —CH(CH₃)—, —CH₂—CH₂—CH₂—, —CH(CH₃)—CH₂—, —CH(CH₂CH₃)—, —CH₂—(CH₂)₂—CH₂—, —CH(CH₃)—CH₂—CH₂—, —CH₂—CH(CH₃)—CH₂—, —CH(CH₃)—CH(CH₃)—, —CH(CH₂CH₃)—CH₂—, —C(CH₃)₂—CH₂—, —CH(CH₂CH₂CH₃)—, —C(CH₃)(CH₂CH₃)—, —CH₂—(CH₂)₃—CH₂—, —CH(CH₃)—CH₂—CH₂—CH₂—, —CH₂—CH(CH₃)—CH₂—CH₂—, —CH(CH₃)—CH₂—CH(CH₃)—, —CH(CH₃)—CH(CH₃)—CH₂—, —C(CH₃)₂—CH₂—CH₂—, —CH₂—C(CH₃)₂—CH₂—, —CH(CH₂CH₃)—CH₂—CH₂—, —CH₂—CH(CH₂CH₃)—CH₂—, —C(CH₃)₂—CH(CH₃)—, —CH(CH₂CH₃)—CH(CH₃)—, —C(CH₃)(CH₂CH₃)—CH₂—, —CH(CH₂CH₂CH₃)—CH₂—, —C(CH₂CH₂CH₃)—CH₂—, —CH(CH₂CH₂CH₂CH₃)—, —C(CH₃)(CH₂CH₂CH₃)—, —C(CH₂CH₃)₂— and —CH₂—(CH₂)₄—CH₂—. The alkylene groups can particularly preferably be selected from the group consisting of —CH₂—, —CH₂—CH₂— and —CH₂—CH₂—CH₂—.

In the context of the present invention, the expression “C₂₋₆-alkenylene group” includes acyclic hydrocarbon radicals having 2, 3, 4, 5 or 6 C atoms which are unsaturated one or more times, for example 2, 3 or 4 times, and can be branched- or straight-chain (unbranched) and unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, by identical or different substituents and which link a corresponding radical to the main general structure. In this context, the alkenylene groups contain at least one C═C double bond. The alkenylene groups can preferably be selected from the group consisting of —CH═CH—, —CH═CH—CH₂—, —C(CH₃)═CH₂—, —CH═CH—CH₂—CH₂—, —CH₂—CH═CH—CH₂—, —CH═CH—CH═CH—, —C(CH₃)═CH—CH₂—, —CH═C(CH₃)—CH₂—, —C(CH₃)═C(CH₃)—, —C(CH₂CH₃)═CH—, —CH═CH—CH₂—CH₂—CH₂—, —CH₂—CH═CH₂—CH₂—CH₂—, —CH═CH═CH—CH₂—CH₂— and —CH═CH₂—CH—CH═CH₂—.

In the context of the invention, the expression “C₂₋₆-alkynylene group” includes acyclic hydrocarbon groups having 2, 3, 4, 5 or 6 C atoms which are unsaturated one or more times, for example 2, 3 or 4 times, and can be branched- or straight-chain (unbranched) and unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, by identical or different substituents and which link a corresponding group to the main general structure. In this context, the alkynylene groups contain at least one C≡C triple bond. The alkynylene groups can preferably be selected from the group consisting of —C≡C—, —C≡C—CH₂—, —C≡C—CH₂—CH₂—, —C≡C—CH(CH₃)—, —CH₂—C≡C—CH₂—, —C≡C—C≡C—, —C≡C—C(CH₃)₂—, —C≡C—CH₂—CH₂—CH₂—, —CH₂—C≡C—CH₂—CH₂—, —C≡C—C≡C—CH₂— and —C≡C—CH₂—C≡C—.

In the context of the present invention, the expression “aryl or heteroaryl group bonded via a C₁₋₃-alkylene group, a C₁₋₆-alkylene group, “C₂₋₆-alkylene group”, C₂₋₆-alkenylene group or C₂₋₆-alkynylene group” means that the C₁₋₃alkylene groups, C₁₋₆-alkylene groups, C₂₋₆-alkylene groups, C₂₋₆-alkenylene groups, C₂₋₆-alkynylene groups and aryl or heteroaryl have the meanings defined above and the aryl or heteroaryl is bonded to the main general structure via a C₁₋₃-alkylene group, C₁₋₆-alkylene group, C₂₋₆-alkylene group, C₂₋₆-alkenylene group or C₂₋₆-alkynylene group. Examples included benzyl, phenethyl and phenylpropyl groups.

In the context of the present invention, the expression “C₃₋₈-cycloalkyl and heterocyclyl bonded via a C₁₋₃-alkylene group, C₁₋₆-alkylene group, C₂₋₆-alkylene group, C₂₋₆-alkenylene group or C₂₋₆-alkynylene group” means that the C₁₋₃-alkylene group, C₁₋₆-alkylene group, C₂₋₆-alkylene group, C₂₋₆-alkenylene group, C₂₋₆-alkynylene group, C₃₋₈-cycloalkyl and heterocyclyl have the meanings defined above and C₃₋₈-cycloalkyl and heterocyclyl is bonded to the main general structure via a C₁₋₃-alkylene group, C₁₋₆-alkylene group, C₂₋₆-alkylene group, C₂₋₆-alkenylene group or C₂₋₆-alkynylene group.

In connection with “alkyl”, “alkylene”, alkenylene”, “alkynylene”, “cycloalkyl” and “heterocyclyl”, in the context of this invention the term “substituted” is understood as meaning replacement of a hydrogen by F, Cl, Br, I, CF₃, OCF₃, CN, NH₂, NH—C₁₋₆-alkyl, NH—C₁₋₆-alkylene-OH, C₁₋₆-alkyl, N(C₁₋₆-alkyl)₂, N(C₁₋₆-alkylene-OH)₂, NO₂, SH, S—C₁₋₆-alkyl, C₁₋₆-alkyl, S-benzyl, O—C₁₋₆-alkyl, OH, O—C₁₋₆-alkylene-OH, ═O, O-benzyl, C(═O)C₁₋₆-alkyl, CO₂H, CO₂—C₁₋₆-alkyl, phenyl, phenoxy, benzyl, naphthyl, furyl, thienyl and pyridinyl, wherein radicals substituted several times are to be understood as meaning those radicals which are substituted several times, for example two or three times, either on different or on the same atoms, for example three times on the same C atom, as in the case of CF₃ or CH₂CF₃, or at different places, as in the case of CH(Cl)—CH═CH—CHC₂. Substitution several times can be by identical or different substituents, such as, for example, in the case of CH(OH)—CH═CH—CHC₂. In particular, this is to be understood as meaning replacement of one or more hydrogens by F, Cl, NH₂, OH, phenyl, O—CF₃ or O—C₁₋₆-alkyl, in particular methoxy.

With respect to “aryl” and “heteroaryl”, in the context of this invention “substituted” is understood as meaning replacement one or more times, for example 2, 3, 4 or 5 times, of one or more hydrogen atoms of the corresponding ring system by F, Cl, Br, I, CN, NH₂, NR^(A)R^(B), C(═O)—NR^(A)R^(B), NH—C₁₋₆-alkyl, NH—C₁₋₆-alkylene-OH, N(C₁₋₆-alkyl)₂, N(C₁₋₆-alkylene-OH)₂, NH-aryl¹, N(aryl¹)₂, N(C₁₋₆-alkyl)aryl¹, pyrrolinyl, piperazinyl, morpholinyl, azetidinyl, piperidinyl, thiazolinyl, azepanyl, diazepanyl, (C₁₋₃-alkylene)-azetidinyl, (C₁₋₃-alkylene)-pyrrolinyl, (C₁₋₃-alkylene)-piperidinyl, (C₁₋₃-alkylene)-morpholinyl, (C₁₋₃-alkylene)-piperazinyl, (C₁₋₃-alkylene)-thiazolinyl, (C₁₋₃-alkylene)-azepanyl, (C₁₋₃-alkylene)-diazepanyl, NO₂, SH, S—C₁₋₆-alkyl, OH, O—C₁₋₆-alkyl, O—C₁₋₆-alkyl-OH, C(═O)C₁₋₆-alkyl, NHSO₂C₁₋₆-alkyl, NHCOC₁₋₆-alkyl, CO₂H, CH₂SO₂-phenyl, CO₂—C₁₋₆-alkyl, OCF₃, CF₃, —O—CH₂—O—, —O—CH₂—CH₂—O—, —O—C(CH₃)₂—CH₂—, unsubstituted C₁₋₆-alkyl, C₃₋₆-cycloalkyl, O—C₃₋₆-cycloalkyl, pyrrolidinyl, imidazolyl, benzyloxy, phenoxy, phenyl, naphthyl, pyridinyl, pyrimidinyl, —C₁₋₃-alkylene-aryl¹, benzyl, thienyl, furyl, or OCF₃, OH, O—C₁₋₆-alkyl, SH, S—C₁₋₆-alkyl, C₃₋₆-cycloalkyl, O—C₃₋₆-cycloalkyl, NR^(A)R^(B), C(═O)—NR^(A)R^(B), phenyl, pyridyl or pyrimidyl bonded via a C₁₋₆-alkylene group, wherein aryl¹ represents phenyl, thiazolyl, thienyl or pyridinyl, on one or various atoms, wherein the above-mentioned substituents—unless stated otherwise—can optionally be substituted in their turn by the substituents mentioned. Substitution of aryl and heteroaryl several times can be by identical or different substituents. Preferred substituents for aryl and heteroaryl can be selected from the group consisting of —O—C₁₋₃-alkyl, unsubstituted C₁₋₆-alkyl, F, Cl, Br, I, CN, CF₃, OCF₃, OH, SH, —CH₂-azetidinyl, —CH₂-pyrrolidinyl, —CH₂-piperidinyl, —CH₂-piperazinyl, —CH₂-morpholinyl, phenyl, naphthyl, thiazolyl, thienyl and pyridinyl, in particular from the group consisting of F, Cl, CN, CF₃, CH₃; OCH₃, OCF₃, and —CH₂-azetidinyl.

In the chemical structural formulae used here to describe the compounds according to the invention, the symbol “

” is also used to describe one or more substitution patterns, this group not being bonded to a particular atom within the chemical structural formula, in contrast to the representation of a bond to a particular atom (by way of example R^(a) here represents a substituent R having a numbering represented by the variable “a”). For example—if the symbol is used in connection with a ring, the particular substituent can be bonded to any possible ring atom.

In the context of the present invention, the symbol

used in formulae designates a linking of a corresponding group to the particular main general structure.

Persons skilled in the art understand that identical atoms or groups that are used for definition of different substituents are in each case independent of one another, such as, for example, in the groupings NR¹⁶R¹⁷, C₁₋₆-alkylene-NR¹⁶R¹⁷, O—C₁₋₆-alkylene-NR¹⁶R¹⁷ and C(═O)—NR¹⁶R¹⁷.

In the context of this invention, the term “physiologically acceptable salt” is understood as meaning preferably salts of the compounds according to the invention with inorganic or organic acids, which are physiologically acceptable—in particular when used on humans and/or mammals. Examples of suitable acids are hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, tartaric acid, mandelic acid, fumaric acid, maleic acid, lactic acid, citric acid, glutamic acid, 1,1-dioxo-1,2-dihydro1λ⁶-benzo[d]isothiazol-3-one (saccharic acid), monomethylsebacic acid, 5-oxo-proline, hexane-1-sulfonic acid, nicotinic acid, 2-, 3- or 4-aminobenzoic acid, 2,4,6-trimethyl-benzoic acid, α-liponic acid, acetylglycine, hippuric acid, phosphoric acid and/or aspartic acid. The salts of hydrochloric acid (hydrochlorides) and of citric acid (citrates) are particularly preferred. This term is furthermore also understood as meaning those compounds which are obtained by quaternization of a nitrogen atom present in the structure (e.g. pyridyl, N-methylpiperidinyl). Such compounds can be obtained, for example, by alkylation with generation of the corresponding cation, with counter-ions such as, for example, Cl⁻ and F⁻.

In the context of the invention, the term isolated used with respect to a stereoisomer—e.g., an enantiomer or diastereomer—means substantially separated from the opposite stereoisomer, but not necessarily from other substances.

In preferred embodiments of the compounds according to the present invention R¹ represents C₁₋₆-alkyl, aryl, heteroaryl, —CH(aryl)₂, C₃₋₈-cycloalkyl or an aryl, heteroaryl or C₃₋₈-cycloalkyl bonded via a C₁₋₆-alkylene group, C₂₋₆-alkenylene group or C₂₋₆-alkynylene group and all the other substituents and indices have the meaning given above.

In preferred embodiments of the compounds according to the invention

-   R^(14a) represents H, NR¹⁶R¹⁷, C₁₋₆-alkylene-NR¹⁶R¹⁷,     O—C₁₋₆-alkylene-NR¹⁶R¹⁷, C(═O)—NR¹⁶R¹⁷, OR¹⁸, C₁₋₆-alkylene-OR¹⁸,     C₁₋₆-alkylene-O—C₁₋₆-alkylene-OR¹⁸, C₁₋₆-alkyl, C₃₋₈-cycloalkyl,     heterocyclyl, aryl or heteroaryl, or denotes a C₃₋₈-cycloalkyl,     heterocyclyl, aryl or heteroaryl group bonded via a C₁₋₆-alkylene     group, and -   R^(14b) represents H, NR¹⁶R¹⁷, C₁₋₆-alkylene-NR¹⁶R¹⁷,     O—C₁₋₆-alkylene-NR¹⁶R¹⁷, C(═O)—NR¹⁶R¹⁷, OR¹⁸, C₁₋₆-alkylene-OR¹⁸,     C₁₋₆-alkylene-O—C₁₋₆-alkylene-OR¹⁸, C₁₋₆-alkyl, C₃₋₈-cycloalkyl,     heterocyclyl, aryl or heteroaryl, or denotes a C₃₋₈-cycloalkyl,     heterocyclyl, aryl or heteroaryl group bonded via a C₁₋₆-alkylene     group,     and all the other substituents and indices have the meaning given     above.

In preferred embodiments of the compounds according to the invention, q represents 0, so that D1 assumes the following form D1′:

In embodiments of the compounds according to the invention which are likewise preferred, s represents 0, so that D2 assumes the following form D2′:

In embodiments of the compounds according to the invention which are furthermore preferred, the partial structure (Ac)

can represent a partial structure which is selected from the group consisting of:

In other preferred embodiments of the compounds according to the present invention the partial structure (Ac) can represent a partial structure which is selected from the group consisting of Ac 1-Ac 32 as defined above.

In embodiments of the compounds according to the invention which are furthermore preferred, the partial structure D1 is selected from the group consisting of

R¹ in the compounds according to the invention preferably represents C₁₋₆-alkyl, —CH(phenyl)₂, C₃₋₈-cycloalkyl, phenyl, naphthyl, chromanyl, indolyl, benzofuranyl, benzothiophenyl (benzothienyl), benzooxazolyl, benzooxadiazolyl, pyrrolyl, furanyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, imidazothiazolyl, carbazolyl, dibenzofuranyl, dibenzothiophenyl (dibenzothienyl) or a phenyl or naphthyl bonded via a C₁₋₃-alkylene group, a C₂₋₃-alkenylene group or a C₂₋₃-alkynylene group, particularly preferably C₁₋₄-alkyl, —CH(phenyl)₂, C₃₋₆-cycloalkyl, phenyl, naphthyl, chromanyl, benzothiophenyl (benzothienyl), benzooxadiazolyl, thienyl, pyridinyl, imidazothiazolyl, dibenzofuranyl or a phenyl bonded via a C₁₋₃-alkylene group or a C₂₋₃-alkenylene group, very particularly preferably C₁₋₄-alkyl, —CH(phenyl)₂, C₃₋₆-cycloalkyl, phenyl, naphthyl, chromanyl, benzothiophenyl (benzothienyl), pyridinyl, thienyl or a phenyl bonded via a C_(1 or 2)-alkylene group or —CH═CH— group, wherein the abovementioned aryl or heteroaryl radicals are in each case unsubstituted or substituted one or more times by identical or different substituents, wherein the substituents independently of one another in particular are selected from the group consisting of —O—C₁₋₃-alkyl, C₁₋₆-alkyl, F, Cl, Br, I, CF₃, OCF₃, OH, SH, phenyl, phenoxy, naphthyl, furyl, thienyl and pyridinyl and wherein the abovementioned alkyl, alkylene, alkenylene and alkynylene groups in each case are unsubstituted or substituted one or more times by identical or different substituents, wherein the substituents independently of one another in particular are selected from the group consisting of —O—C₁₋₃-alkyl, F, Cl, Br, I, CF₃, OCF₃, OH, SH, phenyl, phenoxy, naphthyl, furyl, thienyl and pyridinyl.

In another embodiment R¹ in the compounds according to the invention preferably represents C₁₋₆-alkyl, —CH(phenyl)₂, C₃₋₈-cycloalkyl, phenyl, naphthyl, chromanyl, indolyl, benzofuranyl, benzothiophenyl (benzothienyl), benzooxazolyl, benzooxadiazolyl, pyrrolyl, furanyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazolyl, isoxazolyl, [1,2,3]-thiadiazolyl, pyrazinyl, imidazothiazolyl, carbazolyl, quinoxalinyl, quinolinyl, imidazolyl, benzotriazolyl, dibenzofuranyl, dibenzothiophenyl (dibenzothienyl) or a phenyl or naphthyl bonded via a C₁₋₃-alkylene group, a C₂₋₃-alkenylene group or a C₂₋₃-alkynylene group, or a phenyl or naphthyl bonded via a cyclopropane, cyclobutane, cyclopentane or cyclohexane group; or a C₃₋₈-cycloalkyl group bonded via a C₁₋₃-alkylene group.

Particularly preferably R¹ is C₁₋₆-alkyl, —CH(phenyl)₂, C₃₋₆-cycloalkyl, phenyl, naphthyl, chromanyl, benzothiophenyl (benzothienyl), benzooxadiazolyl, thienyl, pyridinyl, imidazothiazolyl, dibenzofuranyl or a phenyl bonded via a C₁₋₃-alkylene group or a C₂₋₃-alkenylene group, or a phenyl or naphthyl bonded via a cyclopropane, cyclobutane, cyclopentane or cyclohexane group, or a C₃₋₆-cycloalkyl group bonded via a C₁₋₃-alkylene group.

Very particularly preferably R¹ is C₁₋₆-alkyl, —CH(phenyl)₂, C₃₋₆-cycloalkyl, phenyl, naphthyl, chromanyl, benzothiophenyl (benzothienyl), pyridinyl, thienyl or a phenyl bonded via a C_(1 or 2)-alkylene group or —CH═CH— group, or a phenyl bonded via a cyclopropane group, or a C₃₋₆-cycloalkyl group bonded via a C₁₋₃-alkylene group;

wherein the abovementioned aryl or heteroaryl groups are in each case unsubstituted or substituted one or more times by identical or different substituents, wherein the substituents independently of one another in particular are selected from the group consisting of —O—C₁₋₃-alkyl, —S—C₁₋₃-alkyl, C₁₋₆-alkyl, F, Cl, Br, I, CN, CF₃, OCF₃, OH, SH, N(CH₃)₂, NH(CH₃), NH₂, phenyl, phenoxy, naphthyl, furyl, thienyl and pyridinyl, and wherein the abovementioned alkyl, alkylene, alkenylene and alkynylene groups in each case are unsubstituted or substituted one or more times by identical or different substituents, wherein the substituents independently of one another in particular are selected from the group consisting of —O—C₁₋₃-alkyl, F, Cl, Br, I, CF₃, OCF₃, OH, SH, phenyl, phenoxy, naphthyl, furyl, thienyl and pyridinyl.

R¹ can represent in particular —CH(phenyl)₂, phenyl, naphthyl, pyridinyl or thienyl or a phenyl bonded via a C_(1 or 2)-alkylene group or —CH═CH— group, wherein the phenyl, naphthyl, pyridinyl and thienyl is in each case unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, by identical or different substituents chosen from methyl, methoxy, CF₃, OCF₃, F and Cl.

In embodiments of the compounds according to the invention which are likewise preferred, R¹ can be selected from the group consisting of pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 3-chloro-thien-2-yl, 5-chloro-thien-2-yl, 4-methoxy-2,3,6-trimethylphenyl, 4-methoxy-2,6-dimethylphenyl, 4-methoxy-2,3,5-trimethylphenyl, 2,4,6-trimethylphenyl, 2-chloro-6-methylphenyl, 2,4,6-trichlorophenyl, 1,3-dichloro-5-trifluoromethylphenyl, 2-chloro-6-(trifluoromethyl)phenyl, 2,6-dichloro-4-methoxyphenyl, 2,6-dichloro-4-trifluoromethyl, 2-methylnaphthyl, 2-chloronaphthyl, 2-fluoronaphthyl, 2-chloro-4-(trifluoromethoxy)phenyl, 4-chloro-2,5-dimethylphenyl, 2-chloro-6-methylphenyl, 2,3-dichlorophenyl, 3,4-dichlorophenyl, 2,4-dichlorophenyl, 2,4,5-trichlorophenyl, 2,4,6-trichlorophenyl, 2-(trifluoromethyl)phenyl, 3-(trifluoromethyl)phenyl, 4-(trifluoromethyl)phenyl, 1-naphthyl and 2-naphthyl. In particular, R¹ can represent 4-methoxy-2,6-dimethylphenyl or 2-chlorophenyl.

R² in the compounds according to the invention represents H, —CF₃, —CH₂—CF₃, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably H, methyl, ethyl or cyclopropyl. R² particularly preferably represents H.

Preferably, R² in the compounds according to the present invention represents H, —CF₃, —CH₂—CF₃, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably H, methyl, ethyl or cyclopropyl. R² particularly preferably represents H.

In preferred embodiments of the compounds according to the invention, R⁵ and/or R⁶ represent 0 substituents, i.e. are absent.

R⁹ in the compounds according to the invention preferably represents H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, preferably H, methyl, ethyl or cyclopropyl. R⁹ particularly preferably represents H.

Embodiments of the compounds according to the invention which are likewise preferred are those in which the partial structure D2 is selected from the group consisting of

wherein

-   R³⁰⁰ represents 0, 1, 2, 3 or 4 substituents independently selected     from the group consisting of F, Cl, Br, I, —CF₃, —O—CF₃, C₁₋₄-alkyl     and O—C₁₋₄-alkyl; -   R³¹⁰ represents 0, 1, 2 or 3 substituents which independently of one     another are selected from the group consisting of F, Cl, Br, I,     —CF₃, —O—CF₃, C₁₋₄-alkyl and O—C₁₋₄-alkyl; -   R³²⁰ represents a substituent selected from the group consisting of     H, F, Cl, Br, I, —CF₃, —O—CF₃ and C₁₋₄-alkyl; -   R³³⁰ represents a substituent selected from the group consisting of     H, C₁₋₄-alkyl, aryl, —CH₂-aryl and heteroaryl; -   r1 represents 1 or 2, and -   r2 represents 1 or 2.

In embodiments of the compounds according to the invention which are likewise preferred, D2 represents a group selected from the group consisting of:

wherein

-   R³⁰⁰ represents a substituent selected from the group consisting of     H, F, Cl, Br, I, —CF₃, —O—CF₃, C₁₋₄-alkyl and O—C₁₋₄-alkyl; -   R³¹⁰ represents a substituent selected from the group consisting of     H, F, Cl, Br, I, —CF₃, —O—CF₃, C₁₋₄-alkyl and O—C₁₋₄-alkyl; -   R³²⁰ represents a substituent selected from the group consisting of     H, F, Cl, Br, I, —CF₃, —O—CF₃ and C₁₋₄-alkyl, and -   R³³⁰ represents a substituent selected from the group consisting of     H, C₁₋₄-alkyl, aryl, —CH₂-aryl and heteroaryl.

In embodiments of the compounds according to the invention which are furthermore preferred, D2 represents a group selected from the group consisting of:

Embodiments of the substituted spiro-amides according to the invention which are likewise preferred are those in which

-   R^(14a) represents H, aryl, heteroaryl, C₁₋₃-alkylene-aryl or     C₁₋₃-alkylene-heteroaryl; -   R^(14b) represents aryl, heteroaryl, C₁₋₃-alkylene-aryl,     C₁₋₃-alkylene-heteroaryl, NR¹⁶R¹⁷, C₁₋₃-alkylene-NR¹⁶R¹⁷,     C(═O)—NR¹⁶R¹⁷, OR³⁵ or C₁₋₃-alkylene-OR³⁵; -   R¹⁶ and R¹⁷ each independently represent H, methyl, ethyl, n-propyl,     iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl,     cyclobutyl, cyclopentyl or cyclohexyl, or -   R¹⁶ and R¹⁷ together with the nitrogen atom to which they are bound     form a structure selected from the group consisting of

-   R²⁸ represents a substituent selected from the group consisting of     H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,     sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl,     cyclohexyl, aryl and heteroaryl; -   R³³ represents 0, 1 or 2 substituents each independently selected     from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl,     O—C₁₋₃-alkyl and NR^(34a)R^(34b); -   R^(34a) and R^(34b) each independently represent H, methyl, ethyl,     n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,     cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or -   R^(34a) and R^(34b) together with the nitrogen atom joining them     form a group selected from the group consisting of:

-   R³⁹ represents 0, 1 or 2 substituents each independently selected     from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl and     O—C₁₋₃-alkyl; -   R⁴⁰ represents a substituent selected from the group consisting of     H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,     sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl,     cyclohexyl, aryl and heteroaryl; -   R³⁵ represents H, C₁₋₆-alkyl, C₃₋₆-cycloalkyl, aryl, heteroaryl,     C₁₋₃-alkylene-C₃₋₆-cycloalkyl, C₁₋₃-alkylene-aryl,     C₁₋₃-alkylene-heteroaryl or the group

wherein p represents 1, 2 or 3, wherein

-   -   R⁴¹ and R⁴² each independently represent H, methyl, ethyl,         n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,         cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or     -   R⁴¹ and R⁴² together with the nitrogen atom joining them form a         group selected from the group consisting of:

-   R⁴³ represents 0, 1 or 2 substituents each independently selected     from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl,     O—C₁₋₃-alkyl and NR^(45a)R^(45b); -   R⁴⁴ represents a substituent selected from the group consisting of     H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,     sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl,     cyclohexyl, aryl and heteroaryl; -   R^(45a) and R^(45b) each independently represent H, methyl, ethyl,     n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,     cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or -   R^(45a) and R^(45b) together with the nitrogen atom joining them     form a group selected from the group consisting of:

-   R⁴⁶ represents 0, 1 or 2 substituents each independently selected     from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl and     O—C₁₋₃-alkyl; and -   R⁴⁷ represents a substituent selected from the group consisting of     H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,     sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl,     cyclohexyl, aryl and heteroaryl.

Embodiments of the substituted spiro-amides according to the invention which are furthermore preferred are those compounds wherein

-   R¹⁵ represents H, C₁₋₆-alkyl, —CHR²⁵R²⁶, C₁₋₃-alkylene-CHR²⁵R²⁶,     aryl, heteroaryl, C₁₋₃-alkylene-aryl, C₁₋₃-alkylene-heteroaryl,     —C(═O)—R¹⁹, —S(═O)₂—R¹⁹ or the group —C(═O)—N(R²⁰)—R¹⁹; -   R²⁵ and R²⁶ each independently represent H, C₁₋₄-alkyl,     C₃₋₆-cycloalkyl, aryl or heteroaryl, or -   R²⁵ and R²⁶ together with the CH grouping to which they are bound     form a structure selected from the group consisting of

-   R²⁷ represents 0, 1 or 2 substituents each independently selected     from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl,     O—C₁₋₃-alkyl and NR^(48a)R^(48b); -   R^(28a) represents a substituent selected from the group consisting     of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,     sec-butyl, tert-butyl, aryl and heteroaryl; -   R^(48a) and R^(48b) each independently represent H, methyl, ethyl,     n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,     cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, -   R^(48a) and R^(48b) together with the nitrogen atom to which they     are bound form a structure selected from the group consisting of:

-   R⁴⁹ represents 0, 1 or 2 substituents each independently selected     from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl and     O—C₁₋₃-alkyl; -   R⁵² represents a substituent selected from the group consisting of     H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,     sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl,     cyclohexyl, aryl and heteroaryl; -   R¹⁹ represents C₁₋₆-alkyl, aryl, heteroaryl, —CH(aryl)₂,     C₃₋₈-cycloalkyl, heterocyclyl or an aryl, heteroaryl,     C₃₋₈-cycloalkyl or heterocyclyl bonded via a C₁₋₆-alkylene group,     C₂₋₆-alkenylene group or C₂₋₆-alkynylene group; and -   R²⁰ represents H, methyl, ethyl, n-propyl, iso-propyl, n-butyl,     iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl,     cyclopentyl or cyclohexyl.

Further preferred embodiments of the compounds according to the invention are those compounds in which the following partial structure SP

is selected from the group consisting of

wherein

-   R⁸, R^(10a), R¹³, R^(14a), R^(14b), R¹⁵ and R²³ have the     abovementioned meanings, and -   R¹²⁰ represents 0, 1, 2, 3 or 4 substituents independently selected     from the group consisting of F, Cl, OCF₃, CF₃, CN, methyl and     methoxy.

Further preferred embodiments of the compounds according to the invention are those compounds in which the abovementioned partial structure SP is selected from the group consisting of

wherein

-   z represents 1, 2 or 3; -   o1 represents 1; -   R⁶⁰ in each case represents (het)aryl or C₁₋₃-alkylene-(het)aryl; -   R²⁵ and R²⁶ each independently represent H, C₁₋₆-alkyl,     C₃₋₆-cycloalkyl or (het)aryl, or -   R²⁵ and R²⁶ together with the CH grouping to which they are bound     form a structure selected from the group consisting of

-   R²⁷ represents 0, 1 or 2 substituents each independently selected     from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl,     O—C₁₋₃-alkyl and NR^(48a)R^(48b); -   R^(28a) represents a substituent selected from the group consisting     of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,     sec-butyl, tert-butyl and het(aryl); -   R^(48a) and R^(48b) each independently represent H, methyl, ethyl,     n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,     cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, -   R^(48a) and R^(48b) together with the nitrogen atom to which they     are bound form a structure selected from the group consisting of:

-   R⁴⁹ represents 0, 1 or 2 substituents each independently selected     from the group consisting of F, Cl₁, CF₃, OCF₃, C₁₋₆-alkyl and     O—C₁₋₃-alkyl; -   R⁵² represents a substituent selected from the group consisting of     H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,     sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl,     cyclohexyl and (het)aryl; -   G represents C(═O), S(═O)₂ or the group —C(═O)—N(R²⁰), wherein the     nitrogen atom thereof is bonded to R¹⁹, -   R¹⁹ represents C₁₋₆-alkyl, (het)aryl, —CH(aryl)₂, C₃₋₈-cycloalkyl,     heterocyclyl or a (het)aryl, C₃₋₈-cycloalkyl or heterocyclyl bonded     via a C₁₋₆-alkylene group, C₂₋₆-alkenylene group or C₂₋₆-alkynylene     group; -   R²⁰ represents H, methyl, ethyl, n-propyl, iso-propyl, n-butyl,     iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl,     cyclopentyl or cyclohexyl; -   R¹⁶ and R¹⁷ each independently represent H, methyl, ethyl, n-propyl,     iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl,     cyclobutyl, cyclopentyl or cyclohexyl, or -   R¹⁶ and R¹⁷ together with the nitrogen atom to which they are bound     form a structure selected from the group consisting of

-   R²⁸ represents a substituent selected from the group consisting of     H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,     sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl,     cyclohexyl and (het)aryl; -   R³³ represents 0, 1 or 2 substituents each independently selected     from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl,     O—C₁₋₃-alkyl and NR^(34a)R^(34b); -   R^(34a) and R^(34b) each independently represent H, methyl, ethyl,     n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,     cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or -   R^(34a) and R^(34b) together with the nitrogen atom to which they     are bound form a structure selected from the group consisting of:

-   R³⁹ represents 0, 1 or 2 substituents each independently selected     from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl and     O—C₁₋₃-alkyl; -   R⁴⁰ represents a substituent selected from the group consisting of     H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,     sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl,     cyclohexyl, aryl and heteroaryl; -   R³⁵ represents H, C₁₋₆-alkyl, C₃₋₆-cycloalkyl, (het)aryl or a     C₃₋₆-cycloalkyl or (het)aryl bonded via a C₁₋₃-alkylene group; -   R³⁶ represents (het)aryl or C₁₋₃-alkylene-(het)aryl; -   R³⁷ represents H, C₁₋₆-alkyl or for the group

wherein p represents 1, 2 or 3, wherein

-   -   R⁴¹ and R⁴² each independently represent H, methyl, ethyl,         n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,         cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or     -   R⁴¹ and R⁴² together with the nitrogen atom to which they are         bound form a structure selected from the group consisting of:

-   R⁴³ represents 0, 1 or 2 substituents each independently selected     from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl,     O—C₁₋₃-alkyl and NR^(45a)R^(45b); -   R⁴⁴ represents a substituent selected from the group consisting of     H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,     sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl,     cyclohexyl, aryl and heteroaryl; -   R^(45a) and R^(45b) each independently represent H, methyl, ethyl,     n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,     cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or -   R^(45a) and R^(45b) together with the nitrogen atom to which they     are bound form a structure selected from the group consisting of:

-   R⁴⁶ represents 0, 1 or 2 substituents each independently selected     from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl and     O—C₁₋₃-alkyl; -   R⁴⁷ represents a substituent selected from the group consisting of     H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,     sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl,     cyclohexyl, aryl and heteroaryl, and -   het(aryl) in each case represents a structure selected from the     group consisting of:

wherein

-   R¹⁰⁰ represents 0, 1, 2 or 3 substituents each independently     selected from the group consisting of F, Cl, CF₃, OCF₃, OH,     O—C₁₋₆-alkyl, SH, S—C₁₋₆-alkyl, C₁₋₆-alkyl, C₃₋₆-cycloalkyl,     O—C₃₋₆-cycloalkyl, NR⁶¹R⁶², C(═O)—NR⁶¹R⁶², phenyl, pyridyl,     pyrimidyl, or OCF₃, OH, O—C₁₋₆-alkyl, SH, S—C₁₋₆-alkyl,     C₃₋₆-cycloalkyl, O—C₃₋₆-cycloalkyl, NR⁶¹R⁶², C(═O)—NR⁶¹R⁶², phenyl,     pyridyl or pyrimidyl bonded via a C₁₋₆-alkylene group; -   R⁶¹ and R⁶² each independently represent H, C₁₋₆-alkyl or     C₃₋₆-cycloalkyl, or -   R⁶¹ and R⁶² together with the nitrogen atom to which they are bound     form a structure selected from the group consisting of:

-   R⁶³ represents 0, 1 or 2 substituents each independently selected     from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl and     O—C₁₋₃-alkyl; -   R⁶⁴ represents a substituent selected from the group consisting of     H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,     sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl and     cyclohexyl; and -   R³⁵⁰ represents H, CF₃, phenyl, pyridyl, pyrimidyl or a phenyl,     pyridyl or pyrimidyl bonded via a C₁₋₆-alkylene group.

In embodiments of the spiro-amides according to the invention which are also preferred, the abovementioned radical (SP) is selected from the group consisting of

In embodiments of the spiro-amides according to the invention which are furthermore preferred, the abovementioned radical (SP) is selected from the group consisting of

Further embodiments of the compounds according to the invention are those which are represented by the general formulae C1-C16 shown in the following:

wherein the particular radicals, variables and indices have the meanings described herein in connection with the compounds according to the invention and preferred embodiments thereof.

Another preferred embodiment according to the present invention is a compounds corresponding to formula (IA)

wherein the partial structure (Ac)

represents a partial structure selected from the group consisting of:

-   R⁶ represents H or F; -   D represents one of the following groups

-   q represents 0 or 1, preferably 0; -   represents 0 or 1, preferably 0; -   R³⁰⁰ represents F, Cl, Methyl or F₃, -   R³¹⁰ represents F, Cl, Methyl or CF₃, -   R¹ represents C₁₋₆-alkyl, C₃₋₈-cycloalkyl, phenyl, pyridinyl,     benzyl, thienyl, pyrimidinyl, or phenyl bonded via a C₁₋₃-alkylene     group; or phenyl bonded via a C₃₋₆-cycloalkylene group, wherein the     above mentioned aryl or heteroaryl radicals are in each case     unsubstituted or substituted one or more times, e.g. 1, 2, 3 or 4     times, by identical or different substituents, wherein the     substituents independently of one another in particular are selected     from the group consisting of Cl, CF₃, F, Methyl, OCF₃ and OCH₃; -   R² represents H, C₁₋₆-alkyl, unsubstituted or substituted with 1, 2     or 3 F, C₃₋₈-cycloalkyl, preferably H, Cyclopropyl, Methyl,     Isopropyl, tert-Butyl, —CH₂-iso-propyl, —CH₂-tert-Butyl or —CH₂—CF₃;     and     wherein the following partial structure (SP)

is selected from the group

Preferably these aforementioned compounds of formula IA may be the R-Isomers.

Preferably the partial structure (SP) in the aforementioned compounds of formula IA may be selected from the group of (17), (44) and (45).

In the aforementioned compounds of formula IA, R¹ may preferably represent C₁₋₆-alkyl, C₃₋₈-cycloalkyl, phenyl, pyridinyl, benzyl, thienyl, pyrimidinyl, or phenyl bonded via a —C(H)(CH₃)— or —C(CH₃)₂— group, or phenyl bonded via

wherein the above mentioned aryl or heteroaryl groups may each be unsubstituted or substituted one or more times, e.g. 1, 2, 3 or 4 times, by identical or different substituents independently selected from the group consisting of Cl, CF₃, F, Methyl, OCF₃ and OCH₃.

In a further preferred embodiment of the present invention, the substituted compounds according to the invention can be selected from the group consisting of:

-   [H-01]     7-chloro-2-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, -   [H-02]     2-chloro-N-[6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-03]     4-methoxy-2,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [H-04]     2-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.4]nonane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-05]     2-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-06]     N-[6-[9-(azetidin-1-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide, -   [H-07]     2-chloro-N-[6-[9-(3,3-difluoro-azetidin-1-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-08]     2-chloro-N-[6-(9-pyridin-4-yloxy-3-azaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-09]     2-chloro-N-[(1R)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-10]     2-chloro-N-[(1S)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-11]     2-chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-12]     2-chloro-N-[(1S)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-13]     7-chloro-2-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-2,3-dihydro-isoindol-1-one, -   [H-14]     7-chloro-2-[(1R)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-2,3-dihydro-isoindol-1-one, -   [H-15]     7-chloro-2-[(1S)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-2,3-dihydro-isoindol-1-one, -   [H-16]     4-methoxy-2,6-dimethyl-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic     acid amide, -   [H-17]     -methoxy-2,6-dimethyl-N-[(1R)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic     acid amide, -   [H-18]     4-methoxy-2,6-dimethyl-N-[(1S)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic     acid amide, -   [H-19]     4-methoxy-2,6-dimethyl-N-[(1S)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic     acid amide, -   [H-20]     2-chloro-N-[(1S)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-21]     2-chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide

[H-22] 2-chloro-N-[(1R)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,

-   [H-23]     2-chloro-N-[(1S)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide

[H-24] 2-chloro-N-[(1S)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,

-   [H-25]     2-chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [H-26]     2-chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-27]     2-chloro-N-[(1R)-6-(7-pyridin-4-yl-2,7-diazaspiro[3.5]nonane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-28]     2-chloro-N-[(1R)-6-[9-(1-methyl-piperidin-4-yl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-29]     2-chloro-N-[(1R)-6-[9-(4-methyl-piperazine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-31]     2-chloro-N-[(1R)-6-[9-[(1-methyl-piperidin-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-32]     2-chloro-N-[(1R)-6-(spiro[1H-furo[3,4-c]pyridine-3,4′-piperidine]-1′-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-33]     2-chloro-N-[(1R)-6-(8-pyridin-4-yl-4,8-diazaspiro[5.5]undecane-4-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-34]     2-chloro-N-[(1R)-6-(7-pyridin-4-yl-3,7-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-35]     2-chloro-N-[(1R)-6-(2-pyridin-4-yl-2,9-diazaspiro[4.5]decane-9-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-36]     N-[(1R)-6-[9-(4-tert-butyl-piperazin-1-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide, -   [H-37]     2-chloro-N-[(1R)-6-[9-(pyrrolidine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-38]     2-chloro-N-[(1R)-6-[8-(2-pyrrolidin-1-yl-acetyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-39]     2-chloro-N-[6-(8-pyridin-2-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-40]     2-chloro-N-[6-[8-(4-chlorophenyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-41]     2-chloro-N-[6-[8-(4-fluorophenyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-42]     2-chloro-N-[6-[8-[4-(trifluoromethyl)-phenyl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-43]     2-chloro-N-[6-(8-pyridin-3-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-44]     2-chloro-N-[6-(8-pyrimidin-2-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-45]     2-chloro-N-[6-[8-[2-(trifluoromethyl)-pyridin-4-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-46]     2-chloro-N-[6-[8-[8-(trifluoromethyl)-quinolin-4-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-47]     2-chloro-N-[2,2-dimethyl-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide, -   [H-48]     2-chloro-N-[6-[8-[5-(trifluoromethyl)-pyridin-2-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-49]     2-chloro-N-methyl-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-50]     2-chloro-N-[6-(8-isoquinolin-6-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-51]     2-chloro-N-[6-[8-[2-(trifluoromethyl)-pyrimidin-4-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-52]     N-[(5R)-1-Azabicyclo[2.2.2]octan-5-yl]-3-[(3R)-3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-3-azaspiro[5.5]undecane-9-carboxylic     acid amide, -   [H-53]     2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-54]     2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-2,9-diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-55]     2-Chloro-N-[(1R)-6-[9-(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazin-7-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-56]     6-Methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-naphthalene-2-carboxylic     acid amide, -   [H-57]     2-Chloro-N-[(4R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, -   [H-58]     2-Chloro-N-[(4R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, -   [H-59]     2-Chloro-N-[(1R)-5-methyl-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-60]     2-Chloro-4-methoxy-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-61]     4-Methoxy-2-methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-62]     N-[(5S)-1-Azabicyclo[2.2.2]octan-5-yl]-3-[(3R)-3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-3-azaspiro[5.5]undecane-9-carboxylic     acid amide, -   [H-63]     2-Chloro-4-methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-64]     2-Chloro-N-[(1R)-5-fluoro-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide     hydrochloride, -   [H-65]     2-Chloro-N-[(4R)-7-fluoro-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, -   [H-66]     2-Chloro-N-[(1R)-5-methyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-67]     2-Chloro-N-[(4R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, -   [H-68]     6-Methoxy-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-naphthalene-2-carboxylic     acid amide, -   [H-69]     2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-4,8-diazaspiro[5.5]undecane-4-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-70]     2-Chloro-N-[(1R)-7-(2-pyridin-4-yl-2,9-diazaspiro[4.5]decane-9-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-71]     2-Chloro-N-[(1R)-7-(7-pyridin-4-yl-2,7-diazaspiro[3.5]nonane-2-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-72]     2-Chloro-N-[(1R)-7-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-73]     2-Chloro-N-[(4R)-8-fluoro-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, -   [H-74]     2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyloxy)-benzamide, -   [H-75]     2-Methyl-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyloxy)-benzamide, -   [H-76]     2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide, -   [H-77]     2-Chloro-N-[(4R)-8-fluoro-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, -   [H-78]     2-Chloro-N-[(4R)-8-fluoro-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, -   [H-79]     2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.4]nonane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-80]     2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-81]     2-Chloro-N-[(1R)-7-(7-pyridin-4-yl-3,7-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-82]     2-Chloro-N-[(1R)-6-fluoro-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-83]     2-Chloro-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide, -   [H-84]     N-[(1R)-6-(8-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyrimidine-5-carboxylic     acid amide, -   [H-85]     2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide, -   [H-86]     N-[(1R)-6-(3-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyrimidine-5-carboxylic     acid amide, -   [H-87]     2-Chloro-N-[(1R)-6-fluoro-7-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-88]     2-Chloro-N-[(1R)-6-fluoro-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, -   [H-89]     2-Chloro-N-[(1R)-5-fluoro-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-90]     2-Chloro-N-[(1R)-5-fluoro-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-91]     2-Chloro-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-92]     2-Chloro-N-[(4R)-7-fluoro-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, -   [H-93]     2-Chloro-N-[(1R)-5-methyl-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-94]     2,3-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-95]     2,3-Dichloro-N-[(1R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-96]     7-Chloro-2-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, -   [H-97]     2-Chloro-N-[(1R)-6-[9-(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine-7-carbonyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-98]     2,5-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-99]     2,6-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-100]     2,6-Dichloro-N-[(1R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-101]     2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-102]     2-Fluoro-N-[(1R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-103]     4-Methoxy-2,5-dimethyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-104]     2,6-Dimethyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-105]     2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [H-106]     2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic     acid amide, -   [H-107]     2-Chloro-N-[(4R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, -   [H-108]     2-Fluoro-4-methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-109]     2-Chloro-6-fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-110]     2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide, -   [H-111]     2-Chloro-N-[(1R)-6-[8-(2,6-dimethyl-pyridin-4-yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide     hydrochloride, -   [H-112]     2-Chloro-N-[(1R)-6-[8-(2-methyl-pyridin-4-yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-113]     2,3-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [H-114]     2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-3-carboxylic     acid amide, -   [H-115]     N-[(1R)-6-(8-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyl)-pyridine-3-carboxylic     acid amide, -   [H-116]     2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [H-117]     2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [H-118]     N-[(1R)-6-(8-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzenesulfonic     acid amide, -   [H-119]     2,6-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [H-120]     2-Chloro-N-[6-[9-[2-(1H-imidazol-1-yl)-ethoxy]-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-128]     2-Chloro-N-[6-(8-hydroxy-8-pyridin-4-yl-3-azaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-129]     2-Chloro-N-[6-[8-(1-oxido-pyridin-1-ium-4-yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-130]     2-Chloro-N-[6-[8-[5-(trifluoromethyl)-pyrimidin-2-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-131]     2-Chloro-N-[6-[9-(1H-imidazol-1-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-132]     2-Chloro-N-[3,3-dimethyl-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide, -   [H-133]     2-Chloro-N-[6-(8-pyridin-4-yl-3-azaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-134]     5-Methyl-2-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1,2-dihydro-pyrrolo[2,1-e]imidazol-3-one, -   [H-135]     2-Chloro-N-[(1R)-6-(8-pyridin-3-yl-3-azaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-136]     2-Chloro-N-methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [H-137]     2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-N-(2,2,2-trifluoro-ethyl)-benzamide, -   [H-138]     2-Chloro-N-[6-(3-pyridin-4-yl-3,10-diazaspiro[5.6]dodecane-10-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-139]     2-Chloro-N-[(1R)-6-[8-(4-methoxyphenyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-140]     2-Chloro-N-[(1R)-6-[8-(4-cyano-phenyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-141]     2-Chloro-5-fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-142]     2,5-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [H-143]     3-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide, -   [H-144]     4-Methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzenesulfonic     acid amide, -   [H-145]     2-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide, -   [H-146]     2-(2-Chlorophenyl)-2-methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide, -   [H-147]     4-Methoxy-2-methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [H-148]     1-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopropane-1-carboxylic     acid amide, -   [H-149]     2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzenesulfonic     acid amide, -   [H-150]     1-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic     acid amide, -   [H-151]     2-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, -   [H-152]     2-(2-Fluorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, -   [H-153]     2-Chloro-3-fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-154]     2-(o-Tolyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, -   [H-155]     2-Chloro-N-[(1S)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-156]     2-Chloro-N-[(1S)-5-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-157]     7-Chloro-2-[(1S)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, -   [H-158]     7-Chloro-2-[(1S)-5-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, -   [H-159]     7-Chloro-2-[(1R)-5-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, -   [H-160]     7-Chloro-2-[(1R)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, -   [H-161]     2-Chloro-N-[(1S)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-162]     2-Chloro-N-[(1R)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-163]     2-Chloro-N-[(1S)-4-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-164]     2-Chloro-N-[(1R)-4-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-165]     2-Chloro-N-[(1S)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [H-166]     2-Chloro-N-[(1R)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [H-167]     2-Chloro-N-[(1R)-4-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [H-168]     7-Chloro-2-[(1S)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, -   [H-169]     7-Chloro-2-[(1R)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, -   [H-170]     7-Chloro-2-[(1R)-4-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, -   [H-171]     2-Chloro-N-[(1R)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-172]     2-Chloro-N-[(1R)-5-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [H-173]     2-Chloro-N-[(1R)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [Ind_CC-001]     4-methoxy-2,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [Ind_CC-002]     N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic     acid amide, -   [Ind_CC-003]     N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide, -   [Ind_CC-004]     3-chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-005]     5-chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-006]     2,4-dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-007]     2-(2-chlorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, -   [Ind_CC-008]     (E)-3-(2-chlorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acrylamide, -   [Ind_CC-009]     2-(2-chlorophenyl)-2-phenyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, -   [Ind_CC-010]     2-chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [Ind_CC-011]     1-(3,4-dichlorophenyl)-3-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, -   [Ind_CC-012]     1-[(2-chlorophenyl)-methyl]-3-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, -   [Ind_CC-013]     4-methoxy-2,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-014]     N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic     acid amide, -   [Ind_CC-015]     N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide, -   [Ind_CC-016]     3-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-017]     5-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-018]     2,4-dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-019]     2-(2-chlorophenyl)-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, -   [Ind_CC-020]     (E)-3-(2-chlorophenyl)-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acrylamide, -   [Ind_CC-021]     2-(2-chlorophenyl)-N-methyl-2-phenyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, -   [Ind_CC-022]     3-(3,4-dichlorophenyl)-1-methyl-1-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, -   [Ind_CC-023]     3-[(2-chlorophenyl)-methyl]-1-methyl-1-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, -   [Ind_CC-024]     2-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [Ind_CC-025]     4-methoxy-N,2,6-trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [Ind_CC-026]     4-methoxy-N,2,6-trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-027]     N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic     acid amide, -   [Ind_CC-028]     2-(trifluoromethyl)-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-029]     3-chloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-030]     5-chloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-031]     2,4-dichloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-032]     2-(2-chlorophenyl)-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-acetamide, -   [Ind_CC-033]     (E)-3-(2-chlorophenyl)-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-acrylamide, -   [Ind_CC-034]     2-chloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [Ind_CC-035]     4-methoxy-2,6-dimethyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [Ind_CC-036]     1-(3,4-dichlorophenyl)-3-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-urea, -   [Ind_CC-037]     1-[(2-chlorophenyl)-methyl]-3-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-urea, -   [Ind_CC-038]     2-(2-chlorophenyl)-2-phenyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-acetamide, -   [Ind_CC-039]     4-methoxy-2,6-dimethyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-040]     N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic     acid amide, -   [Ind_CC-041]     N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide, -   [Ind_CC-042]     3-chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-043]     5-chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-044]     2,4-dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-045]     2-(2-chlorophenyl)-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, -   [Ind_CC-046]     (E)-3-(2-chlorophenyl)-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acrylamide, -   [Ind_CC-047]     1-(3,4-dichlorophenyl)-3-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, -   [Ind_CC-048]     1-[(2-chlorophenyl)-methyl]-3-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, -   [Ind_CC-049]     2-chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [Ind_CC-050]     4-methoxy-2,6-dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [Ind_CC-051]     2-(2-chlorophenyl)-2-phenyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, -   [Ind_CC-052]     N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-pyridine-2-carboxylic     acid amide, -   [Ind_CC-053]     2-(2-chlorophenyl)-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-acetamide, -   [Ind_CC-054]     5-chloro-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-055]     3-chloro-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-056]     2-(2-chlorophenyl)-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-2-phenyl-acetamide, -   [Ind_CC-057]     1-(3,4-dichlorophenyl)-3-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-urea, -   [Ind_CC-058]     N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-2-(trifluoromethyl)-benzamide, -   [Ind_CC-059]     2,4-dichloro-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide, -   [Ind_CC-060]     (E)-3-(2-chlorophenyl)-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-acrylamide, -   [Ind_CC-061]     1-[(2-chlorophenyl)-methyl]-3-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-urea, -   [Ind_CC-062]     2-chloro-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-benzenesulfonic     acid amide, -   [Ind_CC-063]     N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic     acid amide, -   [Ind_CC-064]     N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-(trifluoromethyl)-benzamide, -   [Ind_CC-065]     3-chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-066]     5-chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-067]     2,4-dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide, -   [Ind_CC-068]     N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-methoxy-2,6-dimethyl-benzamide, -   [Ind_CC-069]     2-(2-chlorophenyl)-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-acetamide, -   [Ind_CC-070]     (E)-3-(2-chlorophenyl)-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-acrylamide, -   [Ind_CC-071]     1-(3,4-dichlorophenyl)-3-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-urea, -   [Ind_CC-072]     2-chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzenesulfonic     acid amide, -   [Ind_CC-073]     1-[(2-chlorophenyl)-methyl]-3-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-urea, -   [Ind_CC-074]     N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-pyridine-2-carboxylic     acid amide, -   [Ind_CC-075]     2-(2-chlorophenyl)-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-phenyl-acetamide, -   [Ind_CC-076]     N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic     acid amide, -   [Ind_CC-077]     2-(2-chlorophenyl)-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, -   [Ind_CC-078]     2,4-dichloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-079]     5-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-080]     3-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-081]     N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide, -   [Ind_CC-082]     2-(2-chlorophenyl)-2-phenyl-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, -   [Ind_CC-083]     (E)-3-(2-chlorophenyl)-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acrylamide, -   [Ind_CC-084]     N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic     acid amide, -   [Ind_CC-085]     1-(3,4-dichlorophenyl)-3-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, -   [Ind_CC-086]     1-[(2-chlorophenyl)-methyl]-3-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, -   [Ind_CC-087]     4-methoxy-2,6-dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [Ind_CC-088]     4-methoxy-2,6-dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-089]     2-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide, -   [Ind_CC-090]     4-methoxy-2,6-dimethyl-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-091]     N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethyl-benzamide, -   [Ind_CC-092]     4-methoxy-2,6-dimethyl-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-093]     N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethyl-benzamide, -   [Ind_CC-094]     4-methoxy-2,6-dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-095]     2-chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-096]     2-chloro-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-097]     2-chloro-N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-098]     2-chloro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-099]     2-chloro-N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-100]     2-chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-101]     2-chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-102]     3-chloro-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-103]     3-chloro-N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-104]     3-chloro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-105]     3-chloro-N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide, -   [Ind_CC-106]     2-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-107]     2-chloro-N-methyl-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-108]     2-chloro-N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide, -   [Ind_CC-109]     2-chloro-N-methyl-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-110]     2-chloro-N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide, -   [Ind_CC-111]     2-chloro-N-methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-112]     2-chloro-N-methyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-113]     2-chloro-N-cyclopropyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-114]     2-chloro-N-cyclopropyl-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-115]     2-chloro-N-cyclopropyl-N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-116]     2-chloro-N-cyclopropyl-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-117]     2-chloro-N-cyclopropyl-N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-118]     2-chloro-N-cyclopropyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-119]     2-chloro-N-cyclopropyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-120]     2-chloro-N-[3-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide, -   [Ind_CC-121]     2-chloro-N-[3-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide, -   [Ind_CC-122]     2-chloro-N-[3-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide, -   [Ind_CC-123]     2-chloro-N-[3-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide -   [Ind_CC-124]     2-chloro-N-[3-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide, -   [Ind_CC-125]     2-chloro-N-[3-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide, -   [Ind_CC-126]     2-chloro-N-[3-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide, -   [Ind_CC-127]     2-chloro-N-[[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, -   [Ind_CC-128]     2-chloro-N-[[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, -   [Ind_CC-129]     2-chloro-N-[[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, -   [Ind_CC-130]     2-chloro-N-[[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, -   [Ind_CC-131]     2-chloro-N-[[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, -   [Ind_CC-132]     2-chloro-N-[[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, -   [Ind_CC-133]     2-chloro-N-[[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, -   [Ind_CC-134]     2-chloro-N-[6-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-yl)-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-135]     2-chloro-N-[6-[2-oxo-2-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-yl)-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-136]     2-chloro-N-[6-[2-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-yl]-2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-137]     2-chloro-N-[6-[2-oxo-2-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-yl]-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-138]     2-chloro-N-[6-[2-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]-undecane-3-yl]-2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-139]     2-chloro-N-[6-[2-oxo-2-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-yl)-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-140]     2-chloro-N-[6-[2-oxo-2-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-yl)-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, -   [Ind_CC-141]     8-chloro-2-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, -   [Ind_CC-142]     8-chloro-2-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, -   [Ind_CC-143]     8-chloro-2-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, -   [Ind_CC-144]     8-chloro-2-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, -   [Ind_CC-145]     8-chloro-2-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, -   [Ind_CC-146]     8-chloro-2-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, -   [Ind_CC-147]     8-chloro-2-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, -   [Ind_CC-148]     8-chloro-4-methyl-2-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one, -   [Ind_CC-149]     8-chloro-4-methyl-2-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one, -   [Ind_CC-150]     8-chloro-2-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methyl-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one, -   [Ind_CC-151]     8-chloro-4-methyl-2-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one, -   [Ind_CC-152]     8-chloro-2-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methyl-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one, -   [Ind_CC-153]     8-chloro-4-methyl-2-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one     and -   [Ind_CC-154]     8-chloro-4-methyl-2-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one -   [IND_CC-200]     2,5-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-201]     2-Chloro-4-methoxy-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-202]     2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-203]     2-Chloro-5-fluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-204]     2-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide -   [IND_CC-205]     2-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide -   [IND_CC-206]     2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-6-(trifluoromethyl)-benzamide -   [IND_CC-207]     2,5-Dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-208]     2,5-Dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-209]     2,5-Dichloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-210]     2,5-Dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide -   [IND_CC-211]     2-Chloro-4-methoxy-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-212]     2-Chloro-4-methoxy-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-213]     2-Chloro-4-methoxy-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-214]     2-Chloro-6-fluoro-3-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-215]     2-Chloro-6-fluoro-3-methyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-216]     2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-6-fluoro-3-methyl-benzamide -   [IND_CC-217]     2-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-218]     2-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-219]     2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-220]     2-Chloro-5-fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-221]     2-Chloro-5-fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-222]     2-Chloro-5-fluoro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-223]     2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-5-fluoro-benzamide -   [IND_CC-224]     2-Chloro-4,5-difluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-225]     2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzamide -   [IND_CC-226]     N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic     acid amide -   [IND_CC-227]     2-Chloro-N,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-228]     2-Chloro-4,5-difluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-229]     2-Chloro-4,5-difluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-230]     2-Chloro-4,5-difluoro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-231]     2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4,5-difluoro-benzamide -   [IND_CC-232]     2-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzamide -   [IND_CC-233]     2-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzamide -   [IND_CC-234]     2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-3-(trifluoromethyl)-benzamide -   [IND_CC-235]     2-Cyano-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-236]     N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic     acid amide -   [IND_CC-237]     N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic     acid amide -   [IND_CC-238]     N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic     acid amide -   [IND_CC-239]     2-Chloro-6-methyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-240]     2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-6-methyl-benzenesulfonic     acid amide -   [IND_CC-241]     2-(2-Chlorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-ethanesulfonic     acid amide -   [IND_CC-242]     2-(2-Chlorophenyl)-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-ethanesulfonic     acid amide -   [IND_CC-243]     2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-6-(trifluoromethyl)-benzamide -   [IND_CC-244]     2,5-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide -   [IND_CC-245]     2,5-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-246]     2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-4-methoxy-benzamide -   [IND_CC-247]     2-Chloro-4-methoxy-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-248]     2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-6-fluoro-3-methyl-benzamide -   [IND_CC-249]     2-Chloro-6-fluoro-3-methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-250]     2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-251]     2-Chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-252]     2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-5-fluoro-benzamide -   [IND_CC-253]     2-Chloro-5-fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-254]     2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-3-(trifluoromethyl)-benzamide -   [IND_CC-255]     2-Chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzamide -   [IND_CC-256]     N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic     acid amide -   [IND_CC-258]     N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic     acid amide -   [IND_CC-259]     2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-6-methyl-benzenesulfonic     acid amide -   [IND_CC-260]     2-(2-Chlorophenyl)-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-ethanesulfonic     acid amide -   [IND_CC-261]     2-Chloro-4-fluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-262]     2-Chloro-4-fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-263]     2-Chloro-4-fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-264]     2-Chloro-6-fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-265]     2,3-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-266]     2,3-Dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-267]     2,3-Dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-268]     2,6-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-269]     2,6-Dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-270]     2,6-Dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-271]     2-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-272]     2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-273]     2-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-274]     2-Chloro-4-fluoro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-275]     2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-fluoro-benzamide -   [IND_CC-276]     2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-4-fluoro-benzamide -   [IND_CC-277]     2-Chloro-4-fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-278]     2-Chloro-6-fluoro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-279]     2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-280]     2-Chloro-6-fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-281]     2,3-Dichloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-282]     2,3-Dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide -   [IND_CC-283]     2,3-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide -   [IND_CC-284]     2,3-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-286]     2,6-Dichloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-287]     2,6-Dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide -   [IND_CC-288]     2,6-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide -   [IND_CC-289]     2,6-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-290]     2-Chloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-291]     2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide -   [IND_CC-292]     2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide -   [IND_CC-293]     2-Chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-294]     2,6-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-295]     2,6-Dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-296]     2-Fluoro-4-methoxy-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-297]     2-Fluoro-4-methoxy-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-298]     2-Fluoro-4-methoxy-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-299]     N,2-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyloxy)-benzamide -   [IND_CC-300]     2-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyloxy)-benzamide -   [IND_CC-301]     5-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide -   [IND_CC-302]     5-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide -   [IND_CC-303]     5-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide -   [IND_CC-304]     2-Fluoro-N,4-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-305]     2-Fluoro-4-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-306]     2-Fluoro-4-methyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-307]     2,6-Dimethyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-308]     N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2,6-dimethyl-benzamide     [IND_CC-309]     N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-2,6-dimethyl-benzamide -   [IND_CC-310]     2,6-Dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-311]     N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-fluoro-4-methoxy-benzamide -   [IND_CC-312]     N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-2-fluoro-4-methoxy-benzamide -   [IND_CC-313]     2-Fluoro-4-methoxy-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-314]     5-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-(trifluoromethyl)-benzamide -   [IND_CC-315]     5-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-2-(trifluoromethyl)-benzamide -   [IND_CC-316]     5-Chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide -   [IND_CC-317]     N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-fluoro-4-methyl-benzamide -   [IND_CC-318]     N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-2-fluoro-4-methyl-benzamide -   [IND_CC-319]     2-Fluoro-4-methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-320]     2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic     acid amide -   [IND_CC-321]     2,6-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-322]     2,6-Dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-323]     2,6-Dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-324]     2,4-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-325]     2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-326]     4-Fluoro-N,2-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-327]     N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic     acid amide -   [IND_CC-328]     N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic     acid amide -   [IND_CC-329]     N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic     acid amide -   [IND_CC-330]     2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic     acid amide -   [IND_CC-331]     2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic     acid amide -   [IND_CC-332]     2,6-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-333]     2,6-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-334]     2,4-Dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-335]     2,4-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-336]     2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-337]     2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-338]     N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-fluoro-2-methyl-benzenesulfonic     acid amide -   [IND_CC-339]     N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-4-fluoro-2-methyl-benzenesulfonic     acid amide -   [IND_CC-340]     N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic     acid amide -   [IND_CC-341]     N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic     acid amide -   [IND_CC-342]     N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic     acid amide -   [IND_CC-343]     2,3-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-344]     2,5-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-345]N,2-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-346]     2-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-347]     2-Methyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-348]     1-(2-Fluorophenyl)-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic     acid amide -   [IND_CC-349]     1-(2-Fluorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic     acid amide -   [IND_CC-350]     1-(2-Fluorophenyl)-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic     acid amide -   [IND_CC-351]     1-(3-Chlorophenyl)-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic     acid amide -   [IND_CC-352]     1-(3-Chlorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic     acid amide -   [IND_CC-353]     1-(3-Chlorophenyl)-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic     acid amide -   [IND_CC-354]     4-Fluoro-N,2,6-trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-355]     4-Fluoro-2,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-356]     4-Fluoro-2,6-dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-357]     2,5-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-358]     2-Methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-359]     1-(2-Fluorophenyl)-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic     acid amide -   [IND_CC-360]     1-(3-Chlorophenyl)-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic     acid amide -   [IND_CC-361]     4-Fluoro-2,6-dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-362]     2,4,5-Trichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-363]     2,4,5-Trichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-364]     N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclohexanecarboxylic     acid amide -   [IND_CC-365]     N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclohexanecarboxylic     acid amide -   [IND_CC-366]     N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclohexanecarboxylic     acid amide -   [IND_CC-367]     N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclohexanecarboxylic     acid amide -   [IND_CC-368]     N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopropanecarboxylic     acid amide -   [IND_CC-369]     N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopropanecarboxylic     acid amide -   [IND_CC-370]     N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopropanecarboxylic     acid amide -   [IND_CC-371]     3,3-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide -   [IND_CC-372]N,3,3-Trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide -   [IND_CC-373]     3,3-Dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide -   [IND_CC-374]     3,3-Dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide -   [IND_CC-375]     N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide -   [IND_CC-376]     2-Fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide -   [IND_CC-377]     2-Fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide -   [IND_CC-378]     2-Fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide -   [IND_CC-379]     4-Fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide -   [IND_CC-380]     4-Fluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide -   [IND_CC-381]     4-Fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide -   [IND_CC-382]     4-Fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide -   [IND_CC-383]     2,6-Difluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-384]     2,6-Difluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-385]     2,6-Difluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-386]     2,6-Difluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-387]N,2,3-Trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-388]     2,3-Dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-389]     2,3-Dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-390]     N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[3-(trifluoromethyl)phenyl]-methanesulfonic     acid amide -   [IND_CC-391]     N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopentanecarboxylic     acid amide -   [IND_CC-392]     N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopentanecarboxylic     acid amide -   [IND_CC-393]     N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopentanecarboxylic     acid amide -   [IND_CC-394]     N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopentanecarboxylic     acid amide -   [IND_CC-395]     N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-pyridine-2-carboxylic     acid amide -   [IND_CC-396]     N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-pyridine-2-carboxylic     acid amide -   [IND_CC-397]     N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyrazine-2-carboxylic     acid amide -   [IND_CC-398]     N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyrazine-2-carboxylic     acid amide -   [IND_CC-399]     2-Fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-400]     2-Fluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-401]     2-Fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-402]     2-Fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-403]     2,6-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic     acid amide -   [IND_CC-404]     2,6-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic     acid amide -   [IND_CC-405]     4-Bromo-2-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-406]     2,4,6-Trichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-407]     2,4,6-Trichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic     acid amide -   [IND_CC-408]N,3-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide -   [IND_CC-409]     3-Methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide -   [IND_CC-410]     N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide -   [IND_CC-411]     N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide -   [IND_CC-412]     3-Cyclopentyl-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide -   [IND_CC-413]     3-Cyclopentyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide -   [IND_CC-414]     N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclobutanecarboxylic     acid amide -   [IND_CC-415]     N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclobutanecarboxylic     acid amide -   [IND_CC-416]N,2-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide -   [IND_CC-417]     2-Methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide -   [IND_CC-418]N,2-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide -   [IND_CC-419]     2-Methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide -   [IND_CC-420]     2-Ethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide -   [IND_CC-500]     2-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-501]     2-Chloro-N-[6-[8-[(2-cyano-phenyl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-502]     2-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-chloro-4-fluoro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic     acid amide -   [IND_CC-503]     2-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-cyano-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic     acid amide -   [IND_CC-504]     2-Chloro-N-[6-[8-[(2,6-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-505]     2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide -   [IND_CC-506]     2-Chloro-N-methyl-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-507]     2-Chloro-N-[6-[9-(1H-pyrrol-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-508]     2-Chloro-N-[6-[9-(1H-imidazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-509]     2-Chloro-N-[6-[9-(pyridin-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-510]     2-Chloro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-511]     2-Chloro-N-[6-[9-(pyridin-3-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-512]     2-Chloro-N-[6-[9-[(1-methyl-1H-pyrrol-2-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-513]     2-Chloro-N-[6-[9-[(2,6-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-514]     2-Chloro-N-[6-[9-[(3,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-515]     2-Chloro-N-[6-[9-[(2,5-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-516]     2-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-517]     2-Chloro-N-[6-[9-[(2-fluoro-6-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-518]     2-Chloro-N-cyclopropyl-N-[6-[8-(pyridin-3-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-519]     2-Chloro-N-cyclopropyl-N-[6-[8-[(1-methyl-1H-pyrrol-2-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-520]     2-Chloro-N-cyclopropyl-N-[6-[8-[(2,6-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-521]     2-Chloro-N-cyclopropyl-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-522]     2-Chloro-N-cyclopropyl-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-523]     2-Chloro-N-cyclopropyl-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-524]     2-Chloro-N-cyclopropyl-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-525]     2-Chloro-N-cyclopropyl-N-[6-[8-[(2-fluoro-6-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-526]     2-Chloro-N-[6-[9-[(3-methyl-3H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-527]     2-Chloro-N-[6-[9-[(5-methyl-3H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-528]     2-Chloro-N-[6-[9-[(2-methyl-1H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-529]     2-Chloro-N-[6-[9-[(2-chloro-4-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-530]     2-Chloro-N-[6-[9-[(2-chloro-6-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-531]     2-Chloro-N-[6-[9-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-532]     2-Chloro-N-[6-[9-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-533]     2-Chloro-N-[6-[9-[(4-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-534]     2-Chloro-N-[6-[9-[(3-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-535]     2-Chloro-N-[6-[9-[(2-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-536]     2-Chloro-N-cyclopropyl-N-[6-[8-[(3-methyl-3H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-537]     2-Chloro-N-[6-[8-[(2-chloro-4-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide -   [IND_CC-538]     2-Chloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide -   [IND_CC-539]     2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide -   [IND_CC-540]     2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide -   [IND_CC-541]     2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide -   [IND_CC-542]     2-Chloro-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-543]     2-Chloro-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-544]     2-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-545]     2-Chloro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-546]     2-Chloro-N-[6-[8-[(2-fluoro-6-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-547]     3-Chloro-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide -   [IND_CC-548]     3-Chloro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide -   [IND_CC-549]     2-Chloro-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide -   [IND_CC-550]     2-Chloro-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide -   [IND_CC-551]     2-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide -   [IND_CC-552]     2-Chloro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide -   [IND_CC-553]     2-Chloro-N-[6-[8-[(5-methyl-3H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-554]     2-Chloro-N-[6-[8-[(2-methyl-1H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-555]     2-Chloro-N-[6-[8-([1,2,3]thiadiazol-4-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-556]     2-Chloro-N-[6-[8-[(2-chloro-4-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-557]     2-Chloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-558]     2-Chloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide -   [IND_CC-559]     2-Chloro-N-[6-[8-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-560]     2-Chloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-561]     2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-562]     2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-563]     2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-564]     2-Chloro-N-[6-[8-[(1,3,5-trimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-565]     2-Chloro-N-[6-[8-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-566]     2-Chloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-567]     2-Chloro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-568]     2-Chloro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-569]     3-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide -   [IND_CC-570]     3-Chloro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide -   [IND_CC-571]     3-Chloro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide -   [IND_CC-572]     2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide -   [IND_CC-573]     2-Chloro-N-[6-[8-(cyclopropanecarbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-574]     2-Chloro-N-[6-[8-(3,3-dimethyl-butanoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-575]     2-Chloro-N-[6-[8-(2-chloro-4-fluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-576]     2-Chloro-N-[6-[8-(2,4-difluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-577]     2-Chloro-N-[6-[8-[2-(4-chlorophenyl)-acetyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-578]     N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide -   [IND_CC-579]     N-[6-[8-(2-tert-Butyl-5-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide -   [IND_CC-580]     N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethyl-benzamide -   [IND_CC-581]     N-[6-[8-(2-tert-Butyl-5-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethyl-benzamide -   [IND_CC-582]     3-Chloro-N-[6-[8-(cyclopropanecarbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide -   [IND_CC-583]     3-Chloro-N-[6-[8-(3,3-dimethyl-butanoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide -   [IND_CC-584]     3-Chloro-N-[6-[8-(2-chloro-4-fluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide -   [IND_CC-585]     3-Chloro-N-[6-[8-(2,4-difluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide -   [IND_CC-586]     3-Chloro-N-[6-[8-[2-(4-chlorophenyl)-acetyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic     acid amide -   [IND_CC-587]     N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3-chloro-thiophene-2-carboxylic     acid amide -   [IND_CC-588]     N-[6-[8-(2-tert-Butyl-5-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3-chloro-thiophene-2-carboxylic     acid amide -   [IND_CC-589]     2-Chloro-N-[6-[8-(cyclopropanecarbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide -   [IND_CC-590]     2-Chloro-N-[6-[8-(3,3-dimethyl-butanoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide -   [IND_CC-591]     2-Chloro-N-[6-[8-(2-chloro-4-fluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide -   [IND_CC-592]     2-Chloro-N-[6-[8-[2-(4-chlorophenyl)-acetyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide -   [IND_CC-593]     N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-N-methyl-benzamide -   [IND_CC-594]     2-Chloro-N-[6-[9-(pyrazine-2-carbonyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-595]     2-Chloro-N-[6-[9-(2-methylsulfanyl-pyridine-3-carbonyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-596]     2-Chloro-N-[6-[9-(4-cyano-benzoyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-597]     2-Chloro-N-[6-[9-(cyclopropanecarbonyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-598]     2-Chloro-N-[6-[9-(3,3-dimethyl-butanoyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-599]     2-Chloro-N-[6-[9-(2-chloro-4-fluoro-benzoyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-600]     2-Chloro-N-[6-[9-(2,4-difluoro-benzoyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-601]     N-[6-[9-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide -   [IND_CC-602]     N-[6-[9-(2-tert-Butyl-5-methyl-2H-pyrazole-3-carbonyl)-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide -   [IND_CC-603]     2-Chloro-N-[6-[8-(cyclopropanecarbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide -   [IND_CC-604]     2-Chloro-N-cyclopropyl-N-[6-[8-(3,3-dimethyl-butanoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-605]     2-Chloro-N-[6-[8-(2-chloro-4-fluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide -   [IND_CC-606]     2-Chloro-N-cyclopropyl-N-[6-[8-(2,4-difluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-607]     N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-N-cyclopropyl-benzamide -   [IND_CC-608]     2-Chloro-N-[6-[9-[(5-chloro-thiophen-2-yl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-609]     2-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-610]     2-Chloro-N-[6-[9-[(3-cyano-4-fluoro-phenyl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-611]     2-Chloro-N-[6-[9-[(2-cyano-phenyl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-612]     2-Chloro-N-[6-[9-[(1-methyl-1H-indol-4-yl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-613]     2-Chloro-N-[6-[9-(isopropylsulfonyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-614]     2-Chloro-N-[6-[9-[(1-methyl-1H-indol-5-yl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-615]     2-Chloro-N-[6-[8-[(5-chloro-thiophen-2-yl)sulfonyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide -   [IND_CC-616]     2-Chloro-N-cyclopropyl-N-[6-[8-[(2,4-difluoro-phenyl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-617]     2-Chloro-N-[6-[8-[(3-cyano-4-fluoro-phenyl)sulfonyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide -   [IND_CC-618]     2-Chloro-N-[6-[8-[(2-cyano-phenyl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide -   [IND_CC-619]     2-Chloro-N-cyclopropyl-N-[6-[8-[(1-methyl-1H-indol-5-yl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-620]     5-Chloro-2-fluoro-N-[6-[8-(1H-pyrrol-2-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-621]     5-Chloro-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide -   [IND_CC-622]     5-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide -   [IND_CC-623]     5-Chloro-2-fluoro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-624]     5-Chloro-2-fluoro-N-[6-[9-(1H-pyrrol-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-625]     5-Chloro-2-fluoro-N-[6-[9-(1H-imidazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-626]     5-Chloro-2-fluoro-N-[6-[9-(pyridin-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-627]     5-Chloro-2-fluoro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-628]     5-Chloro-N-[6-[9-[(3,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide -   [IND_CC-629]     5-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide -   [IND_CC-630]     5-Chloro-2-fluoro-N-[6-[9-[(3-fluoro-4-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-631]     2-Chloro-N-[6-[8-(1H-imidazol-4-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-632]     2-Chloro-N-[6-[8-[(2,6-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-633]     2-Chloro-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-634]     2-Chloro-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-635]     2-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-636]     2-Chloro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-637]     2-Chloro-N-[6-[8-[(2-fluoro-6-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-638]     2-Chloro-N-[6-[9-(1H-pyrrol-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-639]     2-Chloro-N-[6-[9-(1H-imidazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-640]     2-Chloro-N-[6-[9-(pyridin-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-641]     2-Chloro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-642]     2-Chloro-N-[6-[9-(pyridin-3-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-643]     2-Chloro-N-[6-[9-[(1-methyl-1H-pyrrol-2-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide -   [IND_CC-644]     2-Chloro-N-[6-[9-[(2,6-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-645]     2-Chloro-N-[6-[9-[(3,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-646]     2-Chloro-N-[6-[9-[(2,5-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-647]     2-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-648]     2-Chloro-N-[6-[9-[(3-fluoro-4-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide -   [IND_CC-649]     2-Chloro-N-[6-[9-[(2-fluoro-6-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide -   [IND_CC-650]     5-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide -   [IND_CC-651]     5-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide -   [IND_CC-652]     5-Chloro-2-fluoro-N-[6-[9-([1,2,3]thiadiazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-653]     5-Chloro-N-[6-[9-[(4-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide -   [IND_CC-654]     5-Chloro-N-[6-[9-[(3-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide -   [IND_CC-655]     2-Chloro-N-[6-[8-[(5-methyl-3H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-656]     2-Chloro-N-[6-[8-([1,2,3]thiadiazol-4-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-657]     2-Chloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-658]     2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-659]     2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-660]     2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-661]     2-Chloro-N-[6-[9-[(5-methyl-3H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide -   [IND_CC-662]     2-Chloro-N-[6-[9-[(2-methyl-1H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide -   [IND_CC-663]     2-Chloro-N-[6-[9-([1,2,3]thiadiazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-664]     2-Chloro-N-[6-[9-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide -   [IND_CC-665]     2-Chloro-N-[6-[9-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide -   [IND_CC-666]     2-Chloro-N-[6-[9-[(4-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-667]     2-Chloro-N-[6-[9-[(3-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-668]     2-Chloro-N-[6-[9-[(2-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-669]     2-Chloro-N-[6-[9-[(2-chloro-4-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide -   [IND_CC-670]     2-Chloro-N-[6-[9-[(2-chloro-6-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide -   [IND_CC-671]     5-Chloro-2-fluoro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-672]     5-Chloro-2-fluoro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-673]     5-Chloro-2-fluoro-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-674]     5-Chloro-2-fluoro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-675]     5-Chloro-2-fluoro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-676]     5-Chloro-N-[6-[9-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide -   [IND_CC-677]     5-Chloro-2-fluoro-N-[6-[9-(quinolin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-678]     5-Chloro-2-fluoro-N-[6-[9-(quinoxalin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-679]     5-Chloro-2-fluoro-N-[6-[9-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-680]     5-Chloro-2-fluoro-N-[6-[9-(2-methyl-propyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-681]     5-Chloro-2-fluoro-N-[6-(9-phenethyl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-682]     2-Chloro-5-(trifluoromethyl)-N-[6-[8-[(1,3,5-trimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-683]     2-Chloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-684]     2-Chloro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-685]     2-Chloro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-686]     2-Chloro-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-687]     2-Chloro-N-[6-[8-(2-methyl-propyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-688]     2-Chloro-N-[6-[8-(2-ethyl-butyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-689]     2-Chloro-N-[6-[8-(cyclohexyl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-690]     2-Chloro-N-[6-(8-phenethyl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-691]     2-Chloro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-692]     2-Chloro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-693]     2-Chloro-N-[6-[9-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-694]     2-Chloro-N-[6-[9-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-695]     2-Chloro-N-[6-[9-(quinolin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-696]     2-Chloro-N-[6-[9-(quinoxalin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-697]     2-Chloro-N-[6-[9-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-698]     2-Chloro-N-[6-[9-(2-methyl-propyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-699]     2-Chloro-N-[6-[9-(2-ethyl-butyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-700]     2-Chloro-N-[6-[9-(cyclohexyl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-701]     2-Chloro-N-[6-(9-phenethyl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-702]     2-Chloro-N-[6-[9-[3-(3-fluorophenyl)-propyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-703]     2-Chloro-N-[6-[9-[3-(4-fluorophenyl)-propyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide -   [IND_CC-704]     3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-propyl-3,9-diazaspiro[5.5]undecane-9-carboxylic     acid amide -   [IND_CC-705]     3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-cyano-phenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic     acid amide -   [IND_CC-706]     N-Benzyl-3-[3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-3,9-diazaspiro[5.5]undecane-9-carboxylic     acid amide -   [IND_CC-707]     3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(4-dimethylaminophenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic     acid amide -   [IND_CC-708]     3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-cyclohexyl-3,9-diazaspiro[5.5]undecane-9-carboxylic     acid amide -   [IND_CC-709]     3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,6-dichloro-phenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic     acid amide -   [IND_CC-710]     3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,4-dichlorophenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic     acid amide -   [IND_CC-711]     3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,4-difluoro-phenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic     acid amide -   [IND_CC-712]     2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-propyl-2,8-diazaspiro[4.5]decane-8-carboxylic     acid amide -   [IND_CC-713]     2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-chloro-4-fluoro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic     acid amide -   [IND_CC-714]     2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-[4-chloro-2-(trifluoromethyl)-phenyl]-2,8-diazaspiro[4.5]decane-8-carboxylic     acid amide -   [IND_CC-715]     2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-cyano-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic     acid amide -   [IND_CC-716]     N-Benzyl-2-[3-[(2-chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-2,8-diazaspiro[4.5]decane-8-carboxylic     acid amide -   [IND_CC-717]     2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-cyclohexyl-2,8-diazaspiro[4.5]decane-8-carboxylic     acid amide -   [IND_CC-718]     2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,6-dichloro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic     acid amide -   [IND_CC-719]     2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,4-difluoro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic     acid amide -   [IND_CC-720]     2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3,5-difluoro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic     acid amide -   [IND_CC-721]     2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-[(3,4-dichlorophenyl)-methyl]-2,8-diazaspiro[4.5]decane-8-carboxylic     acid amide -   [IND_CC-722]     2,3-Dichloro-N-[6-[8-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-723]     2,3-Dichloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-724]     2,3-Dichloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-725]     2,3-Dichloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-726]     2,3-Dichloro-N-[6-[9-[(2-chloro-4-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-727]     2,3-Dichloro-N-[6-[9-[(2-chloro-6-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-728]     2-Chloro-6-methyl-N-[6-[8-[(2-methyl-1H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-729]     2-Chloro-N-[6-[8-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide -   [IND_CC-730]     2-Chloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide -   [IND_CC-731]     2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide -   [IND_CC-732]     2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide -   [IND_CC-733]     2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide -   [IND_CC-734]     2-Chloro-N-[6-[8-[(2-chloro-4-fluoro-phenyl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide -   [IND_CC-735]     2-Chloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide -   [IND_CC-736]     2-Chloro-6-fluoro-N-[6-[8-[(2-methyl-1H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-737]     2-Chloro-N-[6-[8-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-738]     2-Chloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-739]     2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-740]     2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-741]     2-Chloro-N-[6-[8-[(2-chloro-4-fluoro-phenyl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-742]     2,3-Dichloro-N-[6-[8-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-743]     2,3-Dichloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-744]     2,3-Dichloro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-745]     2,3-Dichloro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-746]     2,3-Dichloro-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-747]     2,3-Dichloro-N-[6-[8-(2-methyl-propyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-748]     2,3-Dichloro-N-[6-[8-(2-ethyl-butyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-749]     2,3-Dichloro-N-[6-(8-phenethyl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-750]     2,3-Dichloro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-751]     2,3-Dichloro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-752]     2,3-Dichloro-N-[6-[9-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-753]     2,3-Dichloro-N-[6-[9-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-754]     2,3-Dichloro-N-[6-[9-(quinolin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-755]     2,3-Dichloro-N-[6-[9-(quinoxalin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-756]     2,3-Dichloro-N-[6-[9-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-757]     2,3-Dichloro-N-[6-[9-(2-methyl-propyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-758]     2,3-Dichloro-N-[6-(9-phenethyl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-759]     2,3-Dichloro-N-[6-[9-[3-(3-fluorophenyl)-propyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-760]     2,3-Dichloro-N-[6-[9-[3-(4-fluorophenyl)-propyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-761]     2-Chloro-6-methyl-N-[6-[8-[(1,3,5-trimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-762]     2-Chloro-N-[6-[8-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide -   [IND_CC-763]     2-Chloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide -   [IND_CC-764]     2-Chloro-6-methyl-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-765]     2-Chloro-6-methyl-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-766]     2-Chloro-6-methyl-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-767]     2-Chloro-6-methyl-N-[6-[8-(2-methyl-propyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-768]     2-Chloro-N-[6-[8-(2-ethyl-butyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide -   [IND_CC-769]     2-Chloro-6-methyl-N-[6-(8-phenethyl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-770]     2-Chloro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide -   [IND_CC-771]     2-Chloro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide -   [IND_CC-772]     2-Chloro-N-[6-[8-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-773]     2-Chloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-774]     2-Chloro-6-fluoro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-775]     2-Chloro-6-fluoro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-776]     2-Chloro-6-fluoro-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-777]     2-Chloro-6-fluoro-N-[6-[8-(2-methyl-propyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-778]     2-Chloro-N-[6-[8-(2-ethyl-butyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-779]     2-Chloro-N-[6-[8-(cyclohexyl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-780]     2-Chloro-6-fluoro-N-[6-(8-phenethyl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-781]     2-Chloro-6-fluoro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-782]     2-Chloro-6-fluoro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-783]     2-Chloro-6-fluoro-N-[6-[9-(1H-pyrrol-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-784]     2-Chloro-6-fluoro-N-[6-[9-(pyridin-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-785]     2-Chloro-6-fluoro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-786]     2-Chloro-6-fluoro-N-[6-[9-(pyridin-3-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-787]     2-Chloro-6-fluoro-N-[6-[9-[(1-methyl-1H-pyrrol-2-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-788]     2-Chloro-N-[6-[9-[(2,6-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-789]     2-Chloro-N-[6-[9-[(3,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-790]     2-Chloro-N-[6-[9-[(2,5-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-791]     2-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-792]     2-Chloro-6-fluoro-N-[6-[9-[(3-fluoro-4-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-793]     2-Chloro-6-fluoro-N-[6-[9-[(2-fluoro-6-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-794]     8-Chloro-2-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methyl-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one -   [IND_CC-795]     8-Chloro-2-[6-[8-[(2-fluoro-6-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methyl-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one -   [IND_CC-796]     2-Chloro-6-fluoro-N-[6-[9-[(3-methyl-3H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-797]     2-Chloro-6-fluoro-N-[6-[9-([1,2,3]thiadiazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-798]     2-Chloro-N-[6-[9-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-799]     2-Chloro-N-[6-[9-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-800]     2-Chloro-N-[6-[9-[(3-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-801]     2-Chloro-N-[6-[9-[(2-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-802]     2-Chloro-N-[6-[9-[(2-chloro-4-fluoro-phenyl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-803]     2-Chloro-N-[6-[9-[(2-chloro-6-fluoro-phenyl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide -   [IND_CC-804]     2-Chloro-N-[6-[2-oxo-2-[8-(quinolin-6-yl-methyl)-3,8-diazaspiro[4.5]decan-3-yl]-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-805]     2-Chloro-N-[6-[2-oxo-2-[8-(quinoxalin-6-yl-methyl)-3,8-diazaspiro[4.5]decan-3-yl]-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-806]     2-Chloro-N-[6-[2-[8-(2-ethyl-butyl)-3,8-diazaspiro[4.5]decan-3-yl]-2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide -   [IND_CC-807]     2-Chloro-N-[6-[2-[8-(cyclohexyl-methyl)-3,8-diazaspiro[4.5]decan-3-yl]-2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide     in the form of the free compounds; of the tautomers; of the     N-oxides; of the racemate; of the enantiomers, diastereomers,     mixtures of the enantiomers or diastereomers or of an individual     enantiomer or diastereomer; or in the form of the salts of     physiologically acceptable acids or bases.

The numbering of the individual embodiments of the compounds according to the invention used above is retained in the following explanations of the present invention, in particular in the description of the examples.

According to one aspect of the present invention, the compounds according to the invention preferably have an antagonistic action on the human B1R receptor or the B1R receptor of the rat. In a preferred embodiment of the invention, the compounds according to the invention have an antagonistic action both on the human B1R receptor (hB1R) and on the B1R receptor of the rat (rB1R).

In a preferred embodiment of the present invention, the compounds according to the invention show an inhibition of at least 15%, 25%, 50%. 70%, 80% or 90% on the human B1R receptor and/or on the B1R receptor of the rat in the FLIPR assay at a concentration of 10 μM. Compounds which show an inhibition on the human B1R receptor and on the B1R receptor of the rat of at least 70%, in particular of at least 80% and particularly preferably of at least 90% at a concentration of 10 μM are very particularly preferred.

The agonistic or antagonistic action of substances can be quantified on the bradykinin receptor 1 (B1R) of the human and rat species with ectopically expressing cell lines (CHO K1 cells) and with the aid of a Ca²⁺-sensitive dyestuff (Fluo-4) in a fluorescent imaging plate reader (FLIPR). The figure in % activation is based on the Ca²⁺ signal after addition of Lys-Des-Arg⁹-bradykinin (0.5 nM) or Des-Arg⁹-bradykinin (100 nM). Antagonists lead to a suppression of the Ca²⁺ inflow after addition of the agonist. % inhibition compared with the maximum achievable inhibition is stated.

The substances according to the invention preferably act, for example, on the B1R relevant in connection with various diseases, so that they are suitable as a pharmaceutical active compound in medicaments.

The invention therefore also provides medicaments containing at least one compound according to the invention and optionally suitable additives and/or auxiliary substances and/or optionally further active compounds.

The medicaments according to the invention optionally contain, in addition to at least one compound according to the invention, suitable additives and/or auxiliary substances, that is to say also carrier materials, fillers, solvents, diluents, dyestuffs and/or binders, and can be administered as liquid medicament forms in the form of injection solutions, drops or juices or as semi-solid medicament forms in the form of granules, tablets, pellets, patches, capsules, plasters/spray-on plasters or aerosols. The choice of auxiliary substances etc. and the amounts thereof to be employed depend on whether the medicament is to be administered orally, perorally, parenterally, intravenously, intraperitoneally, intradermally, intramuscularly, nasally, buccally, rectally or topically, for example on the skin, the mucous membranes or into the eyes. Formulations in the form of tablets, coated tablets, capsules, granules, drops, juices and syrups are suitable for oral administration, and solutions, suspensions, easily reconstitutable dry formulations and sprays are suitable for parenteral, topical and inhalatory administration. Substituted compounds according to the invention in a depot, in dissolved form or in a plaster, optionally with the addition of agents which promote penetration through the skin, are suitable formulations for percutaneous administration. Formulation forms which can be used orally or percutaneously can release the substituted compounds according to the invention in a delayed manner. The substituted compounds according to the invention can also be used in parenteral long-term depot forms, such as e.g. implants or implanted pumps. In principle, other further active compounds known to the person skilled in the art can be added to the medicaments according to the invention.

The amount of active compound to be administered to patients varies as a function of the weight of the patient, of the mode of administration, the indication and the severity of the disease. 0.00005 to 50 mg/kg, in particular 0.01 to 5 mg/kg of at least one compound according to the invention are conventionally administered.

In one form of the medicament, a substituted compound according to the invention contained therein is present as an isolated or pure diastereomer and/or enantiomer, as a racemate or as a non-equimolar or equimolar mixture of the diastereomers and/or enantiomers. Suitable methods for separation of stereoisomers are known to the person skilled in the art.

B1R is involved in particular in the pain event. The substituted compounds according to the invention can accordingly be used in particular for the preparation of a medicament for treatment of pain, in particular acute, visceral, neuropathic or chronic pain or inflammation pain.

The invention therefore also provides the use of at least one substituted compound according to the invention for the preparation of a medicament for treatment of pain, in particular acute, visceral, neuropathic or chronic pain. A particular embodiment of the present invention is the use of at least one of the substituted compounds according to the invention for the preparation of a medicament for treatment of inflammation pain.

The invention also provides the use of at least one substituted compound according to the invention for treatment of pain, in particular acute, visceral, neuropathic or chronic pain or inflammation pain.

The invention also provide the use of at least one substituted compound according to the invention for the preparation of a medicament for treatment of diabetes, diseases of the respiratory tract, for example bronchial asthma, allergies, COPD/chronic obstructive pulmonary disease or cystic fibrosis; inflammatory intestinal diseases, for example ulcerative colitis or CD/Crohn's disease; neurological diseases, for example multiple sclerosis, neurodegenerative diseases, fibrotic diseases, inflammations of the skin, for example atopic dermatitis, psoriasis or bacterial infections; rheumatic diseases, for example rheumatoid arthritis or osteoarthritis; septic shock; reperfusion syndrome, for example following cardiac infarction or stroke, obesity; and as an angiogenesis inhibitor.

The invention also provides the use of at least one substituted compound according to the invention for treatment of one of the abovementioned indications.

In this context, in one of the above uses it may be preferable for a substituted compound which is used to be present as an isolated or pure diastereomer and/or enantiomer, as a racemate or as a non-equimolar or equimolar mixture of the diastereomers and/or enantiomers.

The invention also provides a method for treatment, in particular in one of the abovementioned indications, of a non-human mammal or a human requiring treatment of the appropriate indication by administration of a therapeutically active dose of a substituted compound according to the invention or of a medicament according to the invention.

The invention also provides a method for treatment of pain, in particular one of the abovementioned forms of pain, in a non-human mammal or a human requiring treatment of pain, in particular of acute, visceral, neuropathic or chronic pain or inflammation pain, by administration of a therapeutically active dose of a substituted compound according to the invention, or of a medicament according to the invention.

The present invention also provides a process for the preparation of the substituted spiro-amide compounds according to the invention as described in the description and the examples.

In the following description of the process for preparing the compounds of the invention, references to the respective substituent R groups are intended to correspond to the groups R¹ to R²³ as defined above and/or to the subsequent, more preferred definitions of such substituent groups.

General Process for the Preparation of the Derivatives (IX)

Equation 1: General Process for the Preparation of Substituted Dihydroindenes (IX)

Step (a): Acids corresponding to formula (I) can be prepared by methods known from the literature, e.g. from methyl derivatives by oxidation, e.g. in accordance with: (lit. no. 1) Skraup; Schwamberger; Justus Liebigs Annalen der Chemie; vol. 462; (1928); p. 147, from nitriles by hydrolysis, e.g. in accordance with (lit. no. 2) Moses; Chemische Berichte; vol. 33; (1900); p. 2626, from aryl halides, e.g. in accordance with (lit. no. 3) Gomes, Paulo; Gosmini, Corinne; Perichon, Jacques; Synlett; vol. 10; (2002); p. 1673-1676. and (lit. no. 4) Amatore, Muriel; Gosmini, Corinne; Perichon, Jacques; Journal of Organic Chemistry; vol. 71; (2006); p. 6130-6134, from arylzinc compounds, e.g. in accordance with (lit. no. 5) Takahashi, Hideki; Inagaki, Shinya; Nishihara, Yasushi; Shibata, Takanori; Takagi, Kentaro; Organic Letters; vol. 8; (2006); p. 3037-3040, from aldehydes, e.g. in accordance with (lit. no. 6) Kotake, Yoshihiko; lijima, Atsumi; Yoshimatsu, Kentaro; Tamai, Naoko; Ozawa, Yoichi; et al.; Journal of Medicinal Chemistry; vol. 37; (1994); p. 1616-1624, from arylboronic acids, e.g. in accordance with (lit. no. 7) Horiguchi, Hakaru; Tsurugi, Hayato; Satoh, Tetsuya; Miura, Masahiro; Journal of Organic Chemistry; vol. 73; (2008); p. 1590-1592. Ester derivatives of (I) are optionally obtained by these methods and are then converted into the acids (I) after step (j).

Step (b): Acids corresponding to formula (II) can be prepared from (I) by methods known from the literature, e.g. (lit. no. 8) Horwell, David C.; Howson, William; Nolan, William P. Ratcliffe, Giles S.; Rees, David C.; Willems, Henriette M. G.; Tetrahedron; vol. 51; (1995); p. 203-216. (lit. no. 9) or in accordance with WO2005/87236 (A1).

Step (c): Acids corresponding to formula (II) can be prepared by methods known from the literature, e.g. by oxidation (lit. no. 10) Matveeva, E. D.; Podrugina, T. A.; Zefirova, O, N.; Alekseev, A. S.; Bachurin, S. O.; Pellicciari, R.; Zefirov, N. S.; Russian Journal of Organic Chemistry; vol. 38; (2002); p. 1764-1768, by carbonyl insertion (lit. no. 11) WO2005/95387 (A1) and (lit. no. 12) Takeuchi, Ryo; Yasue, Hiroyuki; Journal of Organic Chemistry; vol. 58; (1993); p. 5386-5392, by oxidation:: (lit. no. 13) Pelliciari, Roberto; Luneia, Roberto; Costantino, Gabriele; Marinozzi, Maura; Natalini, Benedetto; et al.; Journal of Medicinal Chemistry; vol. 38; (1995); p. 3717-3719.

In step (d), acids corresponding to formula (II) are converted by a method known from the literature (cf. (a) Protecting Groups, Philip J. Kocienski, Thieme, Stuttgart; 3rd revised edition (14 Feb. 2005) (b) Protective Groups in Organic Synthesis, Theodora W. Greene and Peter G. M. Wuts, Wiley & Sons; 4th edition (30 Oct. 2006)) into an ester, preferably selected from the group consisting of the methyl, ethyl, isopropyl and tert-butyl ester, corresponding to formula (III).

In step (e), ketones corresponding to formula (III) are reacted in at least one solvent, preferably selected from the group consisting of water, methylene chloride, dimethylformamide, diethyl ether, dioxane, tetrahydrofuran, methanol, ethanol and isopropanol, with a reagent, preferably selected from the group consisting of hydroxylamine, hydroxylamine hydrochloride and N,O-bis(trimethylsilyl)hydroxylamine, optionally in the presence of at least one inorganic base, preferably selected from the group consisting of potassium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, and sodium acetate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, at temperatures of from preferably −15° C. to 100° C. to give compounds with the general formula (IV).

In step (f), hydroxylamines corresponding to formula (IV) are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, chloroform, dimethylformamide, diethyl ether, dioxane, tetrahydrofuran, water, methanol, ethanol and isopropanol, with at least one reducing agent, preferably selected from the group consisting of lithium aluminium hydride, sodium borohydride, lithium borohydride, sodium, sodium amalgam and zinc, optionally in the presence of at least one acid or Lewis acid, preferably selected from the group consisting of hydrochloric acid, sulfuric acid, acetic acid and titanium tetrachloride, at temperatures of from preferably −15° C. to 100° C. to give compounds with the general formula (VI).

In step (f), hydroxylamines corresponding to formula (IV) can optionally also be reacted in at least one solvent, preferably selected from the group consisting of chloroform, ethyl acetate, dimethylformamide, diethyl ether, dioxane, tetrahydrofuran, methanol, ethanol and isopropanol, with hydrogen under pressure of from preferably 1 to 10 bar, in the presence of at least one catalyst, preferably selected from the group consisting of rhodium on charcoal, palladium on charcoal, palladium black, Raney nickel and platinum oxide, optionally in the presence of at least one acid, preferably selected from the group consisting of hydrochloric acid, sulfuric acid and acetic acid, at temperatures of from preferably 0° C. to 50° C. to give compounds with the general formula (VI).

In step (g), amines corresponding to formula (VI) are provided by a method known from the literature (cf. (a) Protecting Groups, Philip J. Kocienski, Thieme, Stuttgart; 3rd revised edition (14 Feb. 2005) (b) Protective Groups in Organic Synthesis, Theodora W. Greene and Peter G. M. Wuts, Wiley & Sons; 4th edition (30 Oct. 2006)) with suitable protective groups (Pg), preferably selected from the group consisting of tert-butyloxycarbonyl (Boc) and benzyl carbamate (Cbz).

In step (h), amines corresponding to formula (VI) or (XII) are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane, tetrahydrofuran, methanol, ethanol and isopropanol, with acid chlorides or sulfonyl chlorides, in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, and optionally with the addition of 4-(dimethylamino)pyridine or 1-hydroxybenzotriazole, at temperatures of from preferably −15° C. to 50° C. to give compounds with the general formula (VII) or (IX).

In step (h), instead of the carboxylic acid chlorides the corresponding carboxylic acids can also optionally be employed. These acids corresponding to formula R¹OH, wherein R¹ has the abovementioned meaning, are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane and tetrahydrofuran, with amines (VI) or (XII), with the addition of at least one coupling reagent, preferably selected from the group consisting of carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDCI), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU), N,N′-dicyclohexylcarbodiimide (DCC) and 1-benzotriazolyloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP), optionally in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, and optionally with the addition of 4-(dimethylamino)pyridine or 1-hydroxybenzotriazole, to give compounds with the general formula (VII) or (IX). Cyclic amidic systems are synthesized in step h) analogously to instructions known from the literature, e.g. (lit. no. 14) Bioorganic & Medicinal Chemistry Letters 17 (2007) 428-433 and (lit. no. 15) Bioorganic & Medicinal Chemistry Letters 17 (2007) 424-427.

In step (i), compounds corresponding to formula (V) or (VII) are reacted in at least one solvent, preferably selected from the group consisting of water, methanol, ethanol, isopropanol, diethyl ether, tetrahydrofuran, toluene, acetonitrile, dimethylformamide, dioxane and dimethylsulfoxide, with an inorganic base, preferably selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, potassium tert-butanolate, lithium propanethiolate and sodium phenylselenolate, optionally with the addition of HMPA or lithium chloride, or with a Lewis acid, preferably selected from the group consisting of trimethylsilyl chloride, boron tribromide and aluminium trichloride, optionally with the addition of thiolene, sodium iodide or lithium chloride, at temperatures of from preferably 0° C. to 100° C. to give compounds corresponding to formula (VIII) or (X).

In step (j), compounds corresponding to formula (X) or (VIII) are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane and tetrahydrofuran, with amines HNR₄R₄′, wherein R₄ and R₄′ have the abovementioned meaning, with the addition of at least one coupling reagent, preferably selected from the group consisting of carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDCI), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU), N,N′-dicyclohexylcarbodiimide (DCC) and 1-benzotriazolyloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP), optionally in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, and optionally with the addition of 4-(dimethylamino)pyridine or 1-hydroxybenzotriazole, to give compounds with the general formula (IX) or (XI).

In step (k), the amine-protecting group (Pg) is split off from molecules corresponding to formula (XI) by a method known from the literature (cf. (a) Protecting Groups, Philip J. Kocienski, Thieme, Stuttgart; 3rd revised edition (14 Feb. 2005) (b) Protective Groups in Organic Synthesis, Theodora W. Greene and Peter G. M. Wuts, Wiley & Sons; 4th edition (30 Oct. 2006)). In particular, for Pg=Boc: In step (k), the compounds corresponding to formula (XI) are reacted in at least one solvent, preferably selected from the group consisting of water, methanol, ethanol, isopropanol, diethyl ether, tetrahydrofuran, acetonitrile, dioxane, dimethylformamide and dimethylsulfoxide, with an acid, preferably selected from the group consisting of trifluoroacetic acid, sulfuric acid and hydrochloric acid, or acetyl chloride/methanol at temperatures of from preferably 0° C. to 80° C. to give compounds with the general formula (XII).

General Process for the Preparation of Spiro-Amines

Educts corresponding to formula (XIII), (XX) and (XXXIII) either are commercially obtainable or can be synthesized by conventional methods known to persons skilled in the art.

In step (o), the amine-protecting group (Pg) is split off from the corresponding compounds by a method known from the literature (cf. (a) Protecting Groups, Philip J. Kocienski, Thieme, Stuttgart; 3rd revised edition (14 Feb. 2005) (b) Protective Groups in Organic Synthesis, Theodora W. Greene and Peter G. M. Wuts, Wiley & Sons; 4th edition (30 Oct. 2006)). In particular, for Pg=Boc: In step (o), the corresponding compounds are reacted in at least one solvent, preferably selected from the group consisting of water, methanol, ethanol, isopropanol, diethyl ether, tetrahydrofuran, acetonitrile, dioxane, dimethylformamide and dimethylsulfoxide, with an acid, preferably selected from the group consisting of trifluoroacetic acid, sulfuric acid and hydrochloric acid, or acetyl chloride/methanol, at temperatures of from preferably 0° C. to 80° C. to give the corresponding deprotected compounds.

Part 1—General Process for the Preparation of the Amines (XV), (XVII) and (XIX)

Equation 2: Preparation of the Amines (XV), (XVII) and (XIX)

In step (l), compounds corresponding to formula (XIII) are reacted in at least one solvent, preferably selected from the group consisting of ethanol, methanol, n-butanol, iso-propanol, 2-butanone, DMSO, diethyl ether, water, benzene, toluene, THF, MC, acetonitrile, acetone, DMF and pentane, with boronic acids, iodide, bromide, chloride or mesylate compounds, optionally with the addition of at least one base, preferably selected from the group consisting of potassium hydroxide, sodium hydroxide, optionally in aqueous or alcoholic solution, potassium carbonate, potassium hexamethyldisilazane, sodium hydride, potassium hydride, sodium methanolate, sodium ethanolate, sodium tert-butylate and diisopropylethylamine, optionally with the addition of an auxiliary substance, preferably selected from the group consisting of 18-crown-6,15-crown-5, terabutylammonium bromide or sulfate, benzyltriethylammonium chloride, 1-n-butyl-3-methylimidazolium tetrafluoroborate and DMAP, optionally using a catalyst, preferably selected from the group consisting of Pd(Pcyclohexyl₃)₂Cl₂, Pd₂(dba)₃, Ni(OAc)₂. Cu(OAc)₂, optionally using a ligand, preferably selected from the group consisting of P(o-tolyl)₃, P(1,1′-bis(diphenylphosphino)ferrocene, 2,2′-bipyridine, P(tri-o-tolylphosphine)₃, to give compounds corresponding to formula (XIV). Compounds corresponding to formula (XIV) are furthermore obtained by reaction of compounds corresponding to formula (XIII) with iodide, bromide, chloride or mesylate compounds under Buchwald-Hartwig conditions.

In step (m), compounds corresponding to formula (XIII) are reacted with aldehydes corresponding to formula R^(b)CHO or ketones corresponding to formula R^(b)COR^(c), wherein R^(b) and R^(c) have the abovementioned meanings, in at least one solvent, preferably from the group consisting of diethyl ether, tetrahydrofuran, methanol, ethanol, dichloroethane, methylene chloride and toluene, with the addition of at least one reducing agent, preferably from the group consisting borane-pyridine complex, sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride and triethylsilane, optionally in the presence of at least one acid, preferably selected from the group consisting of formic acid, acetic acid, hydrochloric acid and trifluoroacetic acid, at temperatures of from preferably −70° C. to 100° C. to give compounds corresponding to formula (XVI).

In step (n), amines corresponding to formula (XIII) are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane, tetrahydrofuran, methanol, ethanol and isopropanol, with acid chlorides R^(d)COCl or sulfonyl chlorides R^(d)SO₂Cl or isocyanates R^(d)NCO, wherein R^(d) has the abovementioned meaning, in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, and optionally with the addition of 4-(dimethylamino)pyridine or 1-hydroxybenzotriazole, at temperatures of from preferably −15° C. to 50° C. to give compounds with the general formula (XVIII).

In step (n), instead of the carboxylic acid chlorides the corresponding carboxylic acids can optionally also be employed. These acids corresponding to formula R^(d)CO₂H, wherein R^(d) has the abovementioned meaning, are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane and tetrahydrofuran, with amines (XIII), with the addition of at least one coupling reagent, preferably selected from the group consisting of carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDCI), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU), N,N′-dicyclohexylcarbodiimide (DCC) and 1-benzotriazolyloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP), optionally in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, and optionally with the addition of 4-(dimethylamino)pyridine or 1-hydroxybenzotriazole, to give compounds with the general formula (XVIII).

Step (o)—See above.

Part 2—General Process for the Preparation of the Amines (XXII), (XXV), (XXVIII), (XXXI) and (XXXII)

Equation 3: Preparation of the Amines (XXII), (XXV), (XXVIII), (XXXI) and (XXXII)

In step (p), compounds corresponding to formula (XX) are reacted with amines corresponding to formula R^(e)NHR^(f), wherein R^(e) and R^(f) have the abovementioned meanings, in at least one solvent, preferably from the group consisting of diethyl ether, tetrahydrofuran, methanol, ethanol, dichloroethane, methylene chloride and toluene, with the addition of at least one reducing agent, preferably from the group consisting borane-pyridine complex, sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride and triethylsilane, optionally in the presence of at least one acid, preferably selected from the group consisting of formic acid, acetic acid, hydrochloric acid and trifluoroacetic acid, at temperatures of from preferably −70° C. to 100° C. to give compounds corresponding to formula (XXI).

In step (q), compounds corresponding to formula (XX) are reacted in at least one organic solvent, preferably from the group consisting of diethyl ether, tetrahydrofuran, methanol, ethanol, dichloroethane, methylene chloride and toluene, with the addition of at least one reducing agent, preferably from the group consisting of lithium aluminium hydride, RedAl® (sodium bis(2-methoxyethoxy)aluminium hydride), lithium tri-tert-butoxyaluminium hydride, sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride, diborane,

and triethylsilane, optionally in the presence of at least one acid, preferably selected from the group consisting of formic acid, acetic acid, hydrochloric acid and trifluoroacetic acid, at temperatures of from preferably −25° C. to 100° C. to give compounds corresponding to formula (XXIII).

In step (r), compounds corresponding to formula (XXIII) are converted, by introduction of a suitable leaving group, such as, for example, halogen or mesylate, and subsequent reaction with alcohols, into compounds corresponding to formula (XXIV). Compounds corresponding to formula (XXII) are converted in at least one solvent, preferably selected from the group consisting of methylene chloride, dioxane, diethyl ether, tetrahydrofuran, acetonitrile and dimethylformamide, with a sulfonyl chloride, preferably selected from the group consisting of methylsulfonyl chloride, trifluoromethylsulfonyl chloride, tolylsulfonyl chloride, and at least one base, preferably selected from the group consisting of cesium carbonate, calcium carbonate, potassium carbonate, triethylamine, diisopropylethylamine and pyridine, at temperatures of from preferably 0° C. to 80° C. into the corresponding mesylates. These are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, dioxane, diethyl ether, tetrahydrofuran, acetonitrile, toluene and dimethylformamide, with a suitable alcohol in the presence of an excess of a base, preferably selected from the group consisting of cesium carbonate, calcium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate, triethylamine, diisopropylethylamine and pyridine, at temperatures of from preferably 0° C. to 80° C. to give compounds corresponding to formula (XXIV). Alternatively, in step (r), compounds corresponding to formula (XXIV) can be prepared from compounds corresponding to formula (XXIV) in a Mitsunobu reaction. Step (r) can moreover be carried out analogously to step (t).

In step (s), the carbonyl compounds (XX) are reacted with metal organyls, typically Li or Mg organyls (Grignard), in solvents, such as, for example, toluene, benzene, hexane, pentane, THF or diethyl ether, optionally with the addition of, for example, CeCl₃, to give the tertiary alcohols (XXVI).

In step (t), in a substitution reaction alcohols corresponding to formula (XXVI) are dissolved in a suitable solvent, such as, for example, ethanol, methanol, n-butanol, iso-propanol, 2-butanone, DMSO, diethyl ether, water, benzene, toluene, THF, MC, acetonitrile, acetone, DMF or pentane or a mixture of these solvents, and a suitable base is added, such as, for example, potassium hydroxide, sodium hydroxide, optionally in aqueous or alcoholic solution, potassium carbonate, potassium hexamethyldisilazane, sodium hydride, potassium hydride, sodium methanolate, sodium ethanolate, sodium tert-butylate or diisopropylethylamine, optionally with the addition of an auxiliary substance, such as, for example, 18-crown-6,15-crown-5, terabutylammonium bromide or sulfate, benzyltriethylammonium chloride, 1-n-butyl-3-methylimidazolium tetrafluoroborate or DMAP, and the reaction is carried out with an iodide, bromide, chloride or mesylate compound.

In step (u), compounds corresponding to formula (XXVI) are reacted in at least one solvent, preferably selected from the group consisting of methanol, ethanol, isopropanol, methylene chloride, dioxane, diethyl ether, dimethylsulfoxide, tetrahydrofuran, acetonitrile and dimethylformamide, in the presence of at least one acid, preferably selected from the group consisting of formic acid, acetic acid hydrochloric acid, sulfuric acid and trifluoroacetic acid, at temperatures of from preferably 0° C. to 100° C. The unsaturated systems formed by this procedure are reduced to the compounds corresponding to formula (XXX) by a method known to the person skilled in the art.

In step (v), compounds corresponding to formula (XXIX) are converted by method A or method B into compounds corresponding to formula (XXXII).

Method A

Compounds corresponding to formula (XXIX) are reacted in an aminal formation reaction by reaction with an amine and 1H-benzotriazole to give the benzotriazole aminal, it being known to the person skilled in the art that the bezotriazole aminal can exist in equilibrium both in the 1H and in the 2H form. Suitable solvents are, for example, benzene, toluene, ethanol, diethyl ether or THF. The use of a Dean-Stark water separator, a molecular sieve or other dehydrating means may be necessary. The reaction time can be between 1 and h at a reaction temperature of from +20° C. to +110° C. The benzotriazole aminal obtained as the intermediate product is then reacted with metal organyls, such as magnesium, zinc or lithium organyls, in organic solvents, for example diethyl ether, dioxane or THF, to give compounds corresponding to formula (XXXII).

Method B

Compounds corresponding to formula (XXIX) are reacted by addition of an amine and a source of cyanide to give nitrile-amines. This reaction can be carried out in one or two steps. In the two-step variant, a nitrile-alcohol is first formed and isolated. The formation of the nitrile-alcohol can be carried out by reaction of compounds corresponding to formula (XXIX) with HCN, KCN or NaCN as the source of cyanide, if NaCN and KCN are used the required cyanide being liberated by the addition of, for example, sodium hydrogen sulfite, sulfuric acid, acetic acid or hydrochloric acid. Preferred solvents are water, methanol, ethanol, THF, piperidine, diethyl ether or a mixture of these solvents. Trimethylsilyl cyanide, for example, is likewise suitable as a source of cyanide; the cyanide can be liberated, for example, by boron trifluoride etherate, InF₃ or HCl. Preferred solvents are water or toluene. (Cyano-C)diethylaluminium, for example, is suitable as a further source of cyanide. THF, toluene or a mixture of the two solvents can be used as the solvent. The reaction temperature for all the variants is preferably between −78° C. and +25° C. Alcohols, such as methanol or ethanol, are particularly suitable as the solvent for the reaction of the nitrile alcohol with the amine to give nitrile-amines. The reaction temperature can be between 0° C. and +25° C. In the one-step variant, the nitrile alcohol primarily formed is formed in situ and reacted with the amine to give nitrile-amines. The nitrile-amine obtained as the intermediate product is then reacted with metal organyls, such as magnesium, zinc or lithium organyls, in organic solvents, for example diethyl ether, dioxane or THF, to give compounds corresponding to formula (XXXII).

Step (o)—See above.

Part 3—General Process for the Preparation of the Amines (XXXVI), (XXXVIII), (XLI) and (XLIV)

Equation 4: Preparation of the Amines (XXXVI), (XXXVIII), (XLI) and (XLIV)

In step (w), the ester corresponding to formula (XXXIII) is reduced by a method known to the person skilled in the art to give the aldehyde corresponding to formula (XXXIV), or the corresponding alcohol is oxidized by a method known to the person skilled in the art to give the aldehyde corresponding to formula (XXXIV).

In step (x), aldehyde corresponding to formula (XXXIV) are reacted by methods known to the person skilled in the art in a Wittig reaction with (methoxymethyl)triphenyl-phosphonium chloride, and a strong base, for example potassium tert-butylate, n-butyllithium, s-butyllithium, phenyllithium, lithium diisopropylamide or lithium hexamethyldisilazide, in organic solvents, for example THF, diethyl ether, cyclohexane, toluene or corresponding mixtures. The aldehydes obtained in this way are then reacted with amines corresponding to formula R^(e)NHR^(f) analogously to step (y) to give compounds corresponding to formula (XXXV).

In step (y), compounds corresponding to formula (XXXIV) are reacted with amines corresponding to formula R^(e)NHR^(f), wherein R^(e) and R^(f) have the abovementioned meanings, in at least one solvent, preferably from the group consisting of diethyl ether, tetrahydrofuran, methanol, ethanol, dichloroethane, methylene chloride and toluene, with the addition of at least one reducing agent, preferably from the group consisting borane-pyridine complex, sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride and triethylsilane, optionally in the presence of at least one acid, preferably selected from the group consisting of formic acid, acetic acid, hydrochloric acid and trifluoroacetic acid, at temperatures of from preferably −70° C. to 100° C. to give compounds corresponding to formula (XXXVII).

In step (z), compounds corresponding to formula (XXXIII) are reacted anologously to the methods described for step (i) to give compounds corresponding to formula (XXXIX).

In step (aa), compounds corresponding to formula (XXXIX) are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane and tetrahydrofuran, with amines corresponding to formula R^(e)NHR^(f), wherein R^(e) and R^(f) have the abovementioned meanings, with the addition of at least one coupling reagent, preferably selected from the group consisting of carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDCI), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU), N,N′-dicyclohexylcarbodiimide (DCC) and 1-benzotriazolyloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP), optionally in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, and optionally with the addition of 4-(dimethylamino)pyridine or 1-hydroxybenzotriazole, to give compounds with the general formula (XL).

In step (aa), compounds corresponding to formula (XXXIX) are optionally reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane and tetrahydrofuran, using at least one coupling reagent, preferably selected from the group consisting of thienyl chloride, oxalyl chloride and phosphoryl chloride, in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, with amines corresponding to formula R^(e)NHR^(f), wherein R^(e) and R^(f) have the abovementioned meanings, to give compounds with the general formula (XL).

In step (ab), carboxylic acid esters or carboxylic acids corresponding to formula (XXXIII) are reacted using suitable reducing agents, such as, for example, LiBH₄, LiAlH₄, Dibal-H, BF₃ etherate, BH₃×DMS or NaBH₄, optionally with the addition of auxiliary reagents, such as, for example, boric acid esters, in an organic solvent, such as THF, MC, toluene, methanol, ethanol, DME, hexane, diethyl ether or mixtures of these solvents, at temperatures of from 0° C. to the reflux temperature, in a reduction the alcohols corresponding to formula (XLII).

In step (ac), compounds corresponding to formula (XXXLII) are reacted anologously to the methods described for steps (r) and (t) to give compounds corresponding to formula (XXXLIII).

Step (o)—See above.

Pharmacological Methods 1. Functional Investigation on the Bradykinin Receptor 1 (B1R)

The agonistic or antagonistic action of substances can be determined on the bradykinin receptor 1 (B1R) of the human and rat species with the following assay. In accordance with this assay, the Ca²⁺ inflow through the channel is quantified with the aid of a Ca²⁺-sensitive dyestuff (type Fluo-4, Molecular Probes Europe BV, Leiden, Holland) in a fluorescent imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA).

2. Method:

Chinese hamster ovary cells (CHO K1 cells) transfected stably with the human B1R gene (hB1R cells) or the B1R gene of the rat (rB1R cells) are used. For functional studies, these cells are plated out on black 96-well plates with a clear base (BD Biosciences, Heidelberg, Germany or Greiner, Frickenhausen, Germany) in a density of 20,000-35,000 cells/well. The cells are left overnight at 37° C. and 5% CO₂ in culture medium (hB1R cells: Nutrient Mixture Ham's F12, Gibco Invitrogen GmbH, Karlsruhe, Germany or DMEM, Sigma-Aldrich, Taufkirchen, Germany; rB1R cells: D-MEM/F12, Gibco Invitrogen GmbH, Karlsruhe, Germany) with 10 vol. % FBS (foetal bovine serum, Gibco Invitrogen GmbH, Karlsruhe, Germany or PAN Biotech GmbH, Aidenbach, Germany). On the following day, the cells are loaded for 60 min at 37° C. with 2.13 μM Fluo-4 (Molecular Probes Europe BV, Leiden Holland) in HBSS buffer (Hank's buffered saline solution, Gibco Invitrogen GmbH, Karlsruhe, Germany) with 2.5 mM probenecid (Sigma-Aldrich, Taufkirchen, Germany) and 10 mM HEPES (Sigma-Aldrich, Taufkirchen, Germany). The plates are then washed 2× with HBSS buffer, and HBSS buffer which additionally contains 0.1% BSA (bovine serum albumin; Sigma-Aldrich, Taufkirchen, Germany), 5.6 mM glucose and 0.05% gelatine (Merck KGaA, Darmstadt, Germany) is added. After a further incubation of 20 minutes at room temperature, the plates are inserted into the FLIPR for the Ca²⁺ measurement. Alternatively, the plates are washed with buffer A (15 mM HEPES, 80 mM NaCl, 5 mM KCl, 1.2 mM CaCl₂, 0.7 mM MgSO₄, 2 g/l glucose, 2.5 mM probenecid), buffer A is added and the plates are loaded with 2.5 μM Fluo-4 and 0.025% Pluronic F127 (Sigma-Aldrich, Taufkirchen, Germany). Thereafter, the cells are washed 2× with buffer A and incubated for 30 minutes at room temperature with buffer A, which additionally contains 0.05% BSA and 0.05% gelatine, and thereafter inserted into the FLIPR for the Ca²⁺ measurement. The Ca²⁺-dependent fluorescence is measured here before and after addition of substances (λ_(ex)=488 nm, λ_(em)=540 nm). Quantification is by measurement of the highest fluorescence intensity (FC, fluorescence counts) over time.

3. FLIPR Assay:

The FLIPR protocol consists of 2 additions of substance. Test substances (10 μM) are first pipetted on to the cells and the Ca²⁺ inflow is compared with the control (hB1R: Lys-Des-Arg⁹-bradykinin >=50 nM; rB1R: Des-Arg⁹-bradykinin 10 μM). This gives the result in % activation based on the Ca²⁺ signal after addition of Lys-Des-Arg⁹-bradykinin (>=50 nM) or Des-Arg⁹-bradykinin (10 μM). After incubation for 10-20 minutes, Lys-Des-Arg⁹-bradykinin (hB1R) or Des-Arg⁹-bradykinin (rB1R) in the concentration of the EC₈₀ is applied and the inflow of Ca²⁺ is likewise determined. Antagonists lead to a suppression of the Ca²⁺ inflow. % inhibition compared with the maximum achievable inhibition is calculated.

For determination of the IC₅₀ value, the substances are added in various concentrations. Duplicate or triplicate determinations (n=2 or n=3) are carried out, and these are repeated in at least one further independent experiment (N>=2).

The compounds preferably have a B1R-antagonistic action on the human receptor and/or on the rat receptor.

The invention is explained in the following with the aid of examples, without limiting the general inventive idea.

EXAMPLES List of Abbreviations

DIBAL-H=diisobutylaluminium hydride eq. equiv.=equivalents h=hours d=days min=minutes Boc=tert-butoxycarbonyl Cbz=benzyloxycarbonyl DMSO=dimethylsulfoxide THF=tetrahydrofuran MC=methylene chloride DMF=dimethylformamide TFA=trifluoroacetic acid wt. %=percent by weight conc.=concentrated sat.=saturated R.t.=retention time

The chemicals and solvents employed were obtained commercially from the conventional suppliers (Acros, Aldrich, Fluka, Lancaster, Maybridge, TCl, Fluorochem, Tyger, ABCR, Fulcrum, FrontierScientific, Milestone etc.). The reactions were carried out in some cases under inert gas (nitrogen). The yields of the compounds prepared are not optimized. The mixing ratios of solvents are always stated in the volume/volume ratio. The equivalent amounts of reagents employed and the amounts of solvent and reaction temperatures and times can vary slightly between different reactions carried out by the same method. The working up and purification methods were adapted according to the characteristic properties of the compounds.

A. Synthesis of the Acid Units 1) Synthesis of the Amino Acid Esters (a) Amino Acid Ester Overview:

A no. Structure Amino acid ester (A) Comments A-01

3-amino-2,3-dihydro-1H-indene-5- carboxylic acid methyl ester (A-01) see below A-02

(3S)-3-amino-2,3-dihydro-1H-indene- 5-carboxylic acid methyl ester (A-02) commercially obtainable from NetChem Company (order no. 517174) A-03

(3R)-3-amino-2,3-dihydro-1H-indene- 5-carboxylic acid methyl ester (A-03) commercially obtainable from NetChem Company (order no. 517173) synthesis see below: step 1 product of A-18 A-04

(3S)-3-amino-2,3-dihydro-1H-indene- 4-carboxylic acid (A-04) commercially obtainable from NetChem Company (order no. 517180) A-05

(3R)-3-amino-2,3-dihydro-1H-indene- 4-carboxylic acid (A-05) commercially obtainable from NetChem Company (order no. 517179) A-06

(8R)-8-amino-5,6,7,8-tetrahydro- naphthalene-2-carboxylic acid methyl ester (A-06) commercially obtainable from NetChem Company (order no. 517119) A-07

(8S)-8-amino-5,6,7,8-tetrahydro- naphthalene-2-carboxylic acid methyl ester (A-07) commercially obtainable from NetChem Company (order no. 517120) A-08

methyl 3-amino-2,2-dimethyl-2,3- dihydro-1H-indene-5-carboxylate (A-08) see below A-09

(R)-methyl 4-aminochroman-6- carboxylate hydrochloride (A-09) commercially obtainable from NetChem Company (order no. 517145) A-11

(R)-methyl 3-amino-6-fluoro-2,3- dihydro-1H-indene-5-carboxylate hydrochloride (A-11) Yield: 86% synthesis analogously to A-14 starting from (R)-3-amino-6- fluoro-2,3-dihydro-1H- indene-5-carboxylic acid hydrochloride (commercially obtainable from NetChem Company (order no. 573243) A-13

(R)-methyl 4-amino-8-fluorochroman- 6-carboxylate hydrochloride (A-13) commercially obtainable from NetChem Company (order no. 572795) A-14

(R)-methyl 8-amino-3-fluoro-5,6,7,8- tetrahydronaphthalene-2-carboxylate hydrochloride (A-14) see below A-15

(R)-methyl 4-amino-7- (trifluoromethyl)chroman-6- carboxylate hydrochloride (A-15) commercially obtainable from NetChem Company (order no. 572943) A-16

methyl 3-amino-1,1-dimethyl-2,3- dihydro-1H-indene-5-carboxylate (A- 16) see below A-17

(R)-methyl 3-(methylamino)-2,3- dihydro-1H-indene-5-carboxylate (A- 17) see below A-18

(R)-methyl 3-(2,2,2- trifluoroethylamino)-2,3-dihydro-1H- indene-5-carboxylale (A-18) see below A-19

(S)-methyl 1-amino-2,3-dihydro-1H- indene-5-carboxylate hydrochloride (A-19) commercially obtainable from NetChem Company (order no. 517172) A-20

(R)-methyl 1-amino-2,3-dihydro-1H- indene-5-carboxylate hydrochloride (A-20) commercially obtainable from NetChem Company (order no. 517171) A-21

(S)-methyl 1-amino-2,3-dihydro-1H- indene-4-carboxylate hydrochloride (A-21) commercially obtainable from NetChem Company (order no. 517168) A-22

(R)-methyl 1-amino-2,3-dihydro-1H- indene-4-carboxylate hydrochloride (A-22) commercially obtainable from NetChem Company (order no. 517167) Note: The following amino acid esters were sometimes employed as as the corresponding HCl salts: A-02, A-03, A-04, A-05, A-06, A-07.

Synthesis of Amino Acid Ester A-01 3-Amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (A-01)

(I) A mixture of 4-(2-carboxyethyl)-benzoic acid (25.7 mmol), anhydrous aluminium trichloride (8 equiv.) and dry sodium chloride (10 wt. % of aluminium chloride) was heated slowly to 190° C. and this was maintained for 1 h. The reaction mixture was then poured on to an ice-water mixture and acidified with 6 N HCl. The aqueous phase was extracted with ethyl acetate and the organic phase was washed successively with water and sat. NaCL solution, dried over Na₂SO₄ and concentrated under reduced pressure to obtain the desired product (2). Yield: 88%

(II) One drop of conc. H₂SO₄ was added to a methanolic solution of the product just obtained in step (I) (0.5 mmol in 15 ml of methanol) and the mixture was heated under reflux for 3 h. The reaction mixture was then cooled to room temperature and concentrated and the residue was taken up in ethyl acetate. The ethyl acetate phase was washed with NaHCO₃ solution, water and sat. NaCl solution, dried over Na₂SO₄ and concentrated under reduced pressure to obtain the desired product (3). Yield: 81.7%

(III) Hydroxylamine hydrochloride (3 equiv.) and sodium acetate (6 equiv.) was added to a methanolic solution (15 ml) of the product just obtained in step (II) (2.8 mmol) and the mixture was heated under reflux under an N₂ atmosphere for 12 h. The reaction mixture was then cooled to room temperature and concentrated and the residue was taken up in ethyl acetate. The ethyl acetate phase was washed with water and sat. NaCl solution, dried over Na₂SO₄ and concentrated under reduced pressure to obtain the desired product (4). Yield: 95%

(IV) Zinc dust (1.2 equiv.) was added to an ethanolic solution (10 ml) of the product just obtained in step (III) (1.4 mmol), water (0.75 ml) and conc. HCl (1.5 ml) and the mixture was refluxed for 2 h. It was then cooled to room temperature, filtered over Celite and concentrated to obtain the desired amine. The crude amine was dissolved in 1,4 dioxane (15 ml) and triethylamine (3 equiv.), and (BOC)₂O (1.5 equiv.) was added. This reaction mixture stirred at room temperature for 2 h and then concentrated and the residue taken up in ethyl acetate. The ethyl acetate phase was washed with water and sat. NaCl solution, dried over Na₂SO₄ and concentrated to obtain the desired product (5). Yield: 76%

(V) Trifluoroacetic acid (2 ml) was added to a solution of the product just obtained in step (IV) (0.4 mmol) in methylene chloride (15 ml) and the mixture was stirred at room temperature for 2 h. The reaction mixture was then concentrated and 2× chloroform was added to the residue and the mixture concentrated to obtain the desired 3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (A-01), which was employed in the subsequent reaction without further purification. Yield: 95% (crude)

Synthesis of Amino Acid Ester A-08 Methyl 3-amino-2,2-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (A-08)

Step 1: A mixture of compound 1 (82.4 mmol, 1.0 eq.), AlCl₃ (593.8 mmol, 7.2 eq.) and NaCl (10% w/w of AlCl₃ used) was heated at 190° C. for 2 h. The reaction mixture was cooled to 25° C., the tacky mass was dissolved in ice-cold water and the solution was shaken with crushed ice in a 5 l glass beaker. A mixture of 600 ml of a 6 N HCl and 750 ml of ethyl acetate was added to the reaction mixture. The organic phase was separated off and the aqueous phase was extracted with ethyl acetate (3×650 ml). The combined organic phases were washed with 2 M HCl (100 ml), water (2×100 ml) and sat. NaCl solution (100 ml) and dried over sodium sulfate. The solvent was concentrated in vacuo in order to obtain the desired product 2. Yield: 90%

Step 2: H₂SO₄ (4 ml) was added to a solution of compound 2 (14 g, 79.5 mmol) in MeOH (100 ml) and the reaction mixture was heated under reflux for 3 h. The solvent was concentrated in vacuo, the residue was dissolved in water and the solution was rendered basic with sat. NaHCO₃ solution and extracted with ethyl acetate (2×600 ml). The combined organic phases were washed with water (2×150 ml) and sat. NaCl solution (2×50 ml) and dried over sodium sulfate. The solvent was concentrated in vacuo and the residue was purified by column chromatography (silica gel, 15% ethyl acetate in hexane) in order to obtain the desired ester 3. Yield: 66%

Step 3: A solution of compound 3 (36.38 mmol, 1.0 eq.) in abs. THF (50 ml) was added to a stirred suspension of NaH (2.2 eq.) in THF (50 ml) at 0° C. and the reaction mixture obtained was stirred at 25° C. for 30 min. The reaction mixture was cooled to 0° C., methyl iodide (254.66 mmol, 7.0 eq.) was added and the mixture was stirred at 25° C. for 2 h The reaction mixture was quenched with ice-water (50 ml and extracted with ethyl acetate (200 ml). The organic phase is washed with water (100 ml) and sat. NaCl solution (100 ml) and dried over sodium sulfate. The solvent was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 15% ethyl acetate in hexane) in order to obtain the desired dimethylated product 4. Yield: 66%

Step 4: NH₂OH.HCl (60.54 mmol, 2.2 eq.) and CH₃COONa (121.08 mmol, 4.4 eq.) were added to a solution of compound 4 (27.52 mmol, 1.0 eq.) in methanol (50 ml) and the reaction mixture was heated under reflux for 6 h. When the reaction was complete (TLC control), the solvent was concentrated in vacuo, the residue was dissolved in ethyl acetate (300 l) and the solution was washed with water (2×100 ml) and sat. NaCl solution (2×100 ml). The organic phase was dried over sodium sulfate and the solvent was concentrated in vacuo in order to obtain the crude product, which was employed in the next step without further purification. Yield: 92%

Step 5: Conc. HCl (35 ml) was added to a solution of compound 5 (27.0 mmol, crude) in EtOH:H₂O (10:1, 220 ml). Zn dust (20 g) was added to the reaction mixture in portions and the mixture was heated under reflux for 2 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product 6, which was employed in the next step without further purification. Yield: 40 g (crude)

Synthesis of Amino Acid Ester A-14 (R)-Methyl 8-amino-3-fluoro-5,6,7,8-tetrahydronaphthalene-2-carboxylate hydrochloride (A-14)

Step-1: (R)-8-Amino-3-fluoro-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride (commercially obtainable from NetChem Company (order no. 573545)) (2.035 mmol, 1 eq.) was added to a solution of HCl in methanol (1.25 M, 15 eq.) and the resulting mixture was heated to reflux for 16 h. The solvent was concentrated in vacuo, and the residue was dissolved in acetone (5 ml) and diethyl ether (30 ml) was added. The white solid was collected by filtration, washed with diethyl ether and dried in vacuo. Yield: 95%

Synthesis of Amino Acid Ester A-16 Methyl 3-amino-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (A-16)

Step-1: 6-Bromo-3,3-dimethyl-2,3-dihydro-1H-inden-1-one

Bromine (0.2 ml, 3.8 mmol, 1.2 eq.) was added to a mixture of AlCl₃ (1.04 g, 7.8 mmol, 2.5 eq.) and 3,3-dimethyl-indan-1-one (500 mg, 3.1 mmol) at 100° C. and the reaction mixture was heated at same temperature for 40-45 min. TLC (10% ethyl acetate/hexanes) showed the major product formation with little starting material and dibromo product. The reaction mass was quenched with crushed ice and extracted with ethyl acetate (3×50 ml). The organic part was separated, dried over Na₂SO₄ and evaporated under reduced pressure. The crude compound was purified by column chromatography (silica gel, 10% ethyl acetate/hexanes) to give the desired compound as a pale yellow solid. Yield: 27% (280 mg, 0.85 mmol).

Step-2: Methyl 1,1-dimethyl-3-oxo-2,3-dihydro-1H-indene-5-carboxylate

6-Bromo-3,3-dimethyl-2,3-dihydro-1H-inden-1-one (2 g, 8.36 mmol, 1.0 eq.) was taken up a mixture of DMSO (45 ml) and methanol (30 ml). The reaction mixture was degassed with argon for 15 min and then palladium acetate (80 mg, 0.35 mmol, 0.04 eq.) and dppp (1,3-bis-diphenylphosphino propane) (160 mg, 0.38 mmol, 0.04 eq.) was added and it was degassed with CO for 30 min. The reaction mixture was stirred at 65° C. under CO balloon pressure for 2 h. Methanol was evaporated under reduced pressure, the resulting solution was diluted with water (100 ml) and extracted with diethyl ether (3×25 ml). The organic layer was dried over sodium sulfate and the filtrate was concentrated to give the crude product which was purified by column chromatography (silica gel, 10% ethyl acetate/hexanes) to yield the desired product as a pale yellow solid. Yield: 45% (820 mg, 3.76 mmol).

Step-3: Methyl 3-(hydroxyimino)-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate

To a stirred solution of methyl 1,1-dimethyl-3-oxo-2,3-dihydro-1H-indene-5-carboxylate (430 mg, 1.97 mmol, 1.0 eq.) in methanol (7.5 ml) was added hydroxylamine hydrochloride (340 mg, 4.93 mmol, 2.5 eq.) followed by sodium acetate (807 mg, 9.85 mmol, 5.0 eq.) and the reaction mixture was heated at reflux for 2 h at 80° C. The reaction mixture was concentrated and then extracted with ethyl acetate (3×40 ml). The organic part was separated, washed with water (20 ml) and brine (20 ml) and dried over sodium sulfate. After concentrating the filtrate the crude product thus obtained was directly taken through to the next step without purification.

Step-4: Methyl 3-(tert-butoxycarbonylamino)-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate

Conc. HCl (2 ml) and water (1 ml) were added to a stirred solution of methyl 3-(hydroxyimino)-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (350 mg, 1.5 mmol, 1 eq.) in ethanol (3 ml) and the reaction mixture was stirred for 15 min. Zinc powder (640 mg, 100 mmol, 67 eq.) was added portionwise and the reaction mixture was stirred until complete conversion had taken place. The mixture was filtered through a sintered funnel and the residue washed with ethanol. The filtrate was concentrated to give the crude amine (1 g; crude), which was dissolved, in dioxane (100 ml). The mixture was cooled to 5-10° C. and triethylamine (3.3 ml, 32.8 mmol) was added, followed by boc anhydride (500 mg, 2.3 mmol, 2 eq.), which was added slowly. The reaction mixture was stirred at room temperature for 12 h. The mixture was concentrated to dryness under reduced pressure and ethyl acetate (100 ml) and water (100 ml) were added. The organic part was separated, washed with water (20 ml) and brine (20 ml), and dried over sodium sulfate. The solvent was removed under reduced pressure to give the crude product which was purified by column chromatography (silica gel, 0-5% MeOH/MC) to yield the desired product as a colorless semisolid. Yield: 52% (250 mg, 0.78 mmol).

Step-5: Methyl 3-amino-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate

TFA (0.7 ml, 9 mmol, 13 eq.) was added to a stirred solution of methyl 3-(tert-butoxycarbonylamino)-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (220 mg, 0.69 mmol, 1 eq.) in methylene chloride (10 ml) at 0° C. and the mixture was stirred at RT for 2 h. After complete deprotection (checked by TLC) the solvent was removed under reduced pressure. The residue was diluted with methylene chloride (50 ml) and washed with water (10 ml) and brine (10 ml). The organic part was evaporated under reduced pressure to give the crude product which was directly used for the next step without further purification.

Synthesis of Amino Acid Ester A-17 (R)-Methyl 3-(methylamino)-2,3-dihydro-1H-indene-5-carboxylate (A-17)

Step-1: (R)-tert-Butyl 6-bromo-2,3-dihydro-1H-inden-1-ylcarbamate

To a mixture of (R)-6-bromo-2,3-dihydro-1H-inden-1-amine (5.0 g, 20.16 mmol, 1.0 eq.) in methylene chloride (100 ml) and TEA (11.20 ml, 80.64 mmol, 4.0 eq.) was added dropwise boc-anhydride (6.47 ml, 30.24 mmol, 1.5 eq.) at 00° C. and the mixture was then stirred at RT for 16 h. After completion of the reaction (monitored by TLC) the mixture was diluted with methylene chloride (100 ml) and the organic layer was washed with water (100 ml) and brine (100 ml), and dried over anhydrous Na₂SO₄. The solvent was evaporated to afford the desired product as a brown solid which was used in the next step without further purification.

Step-2: (R)-Methyl 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylate

A solution of (R)-tert-butyl 6-bromo-2,3-dihydro-1H-inden-1-ylcarbamate (15.0 g, 48.07 mmol, 1.0 eq.) in a mixture of MeOH (200 ml) and DMSO (30 ml) was degassed with argon for 30 min followed by addition of palladium acetate (0.53 g, 2.40 mmol, 0.05 eq.), 1,3-bis(diphenylphosphino)propane (0.99 g, 2.40 mmol, 0.05 eq.) and TEA (20 ml, 144.21 mmol, 3.0 eq.). The reaction mixture was then sealed in an autoclave using CO pressure (80 psi) and heated at 75° C. for 16 h. The mixture was evaporated to dryness, diluted with water (150 ml) and extracted with ethyl acetate (2×300 ml). The combined organic layers were washed with brine (100 ml), dried over anhydrous Na₂SO₄ and evaporated to give the crude product which was purified by column chromatography (silica gel; 5% ethyl acetate/hexanes) to yield the desired product as a white solid. Yield: 76% (10.6 g, 36.43 mmol).

Step-3: (R)-Methyl 3-(tert-butoxycarbonyl(methyl)amino)-2,3-dihydro-1H-indene-5-carboxylate

A solution of (R)-methyl 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylate (600 mg, 2.062 mmol, 1.0 eq.) in dry DMF (2 ml) was added to a stirred suspension of NaH (118 mg, 2.474 mmol, 1.2 eq., 50% in mineral oil) in DMF (3 ml) at 0° C. MeI (322 μl, 5.15 mmol, 2.5 eq.) was added to the reaction mixture at same temperature and it was stirred at RT for 2 h. After completion of the reaction (monitored by TLC), the reaction mixture diluted with ice-cold water (50 ml) and extracted with ethyl acetate (2×50 ml). The combined organic layers were washed with water (50 ml) and brine (50 ml), and dried over sodium sulfate. The solvent was evaporated under reduced pressure to give the crude product as a brown sticky solid which was used in the next step without further purification. Yield: 90% (566 mg, 1.855 mmol).

Step-4: (R)-Methyl 3-(methylamino)-2,3-dihydro-1H-indene-5-carboxylate (A-17)

TFA (2 ml) was added dropwise to a solution of (R)-methyl 3-(tert-butoxycarbonyl(methyl)-amino)-2,3-dihydro-1H-indene-5-carboxylate (760 mg, 2.49 mmol, 1.0 eq.) in methylene chloride (10 ml) at 0° C. The reaction mixture was then stirred at RT for 2 h. After completion of the reaction, the reaction mixture was concentrated to afford the desired product which was used in the next step without further purification.

Synthesis of Amino Acid Ester A-18 (R)-Methyl 3-(2,2,2-trifluoroethylamino)-2,3-dihydro-1H-indene-5-carboxylate (A-18)

Step-1: (3R)-3-Amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (A-03)

TFA (10 ml) was added dropwise to a solution of (R)-methyl 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylate (see step-2 product of A-17) (2.0 g, 6.87 mmol, 1.0 eq.) in methylene chloride (30 ml) at 0° C. The reaction mixture was then stirred at RT for 1 h. After completion (monitored by TLC), the reaction mixture was evaporated to afford the desired product as a colorless gummy solid which was used in the next step without further purification.

Step-2: (R)-Methyl 3-(2,2,2-trifluoroacetamido)-2,3-dihydro-1H-indene-5-carboxylate

To a solution of (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (A-03) (2.09 g, 6.87 mmol, 1.0 eq.) in methylene chloride (30 ml) was added dropwise TEA (2.86 ml, 20.61 mmol, 3.0 eq.) at 0° C. and it was stirred for 15 min. Trifluoroacetic anhydride (1.05 ml, 7.56 mmol, 1.1 eq.) was then added dropwise at 0° C. and the reaction mixture was stirred at RT for 12 h. After completion of the reaction (monitored by TLC), the mixture was diluted with methylene chloride (200 ml) and the organic layer was washed with water (50 ml) and brine (50 ml), and dried over anhydrous Na₂SO₄. The solvent was evaporated to afford the crude product which was purified by column chromatography (silica gel; 7% ethyl acetate/hexanes) to yield the desired compound as a white solid. Yield: 92% (1.8 g, 6.27 mmol).

Step-3: (R)-Methyl 3-(2,2,2-trifluoroethylamino)-2,3-dihydro-1H-indene-5-carboxylate (A-18)

To a cooled (0° C.) solution of (R)-methyl 3-(2,2,2-trifluoroacetamido)-2,3-dihydro-1H-indene-5-carboxylate (1.8 g, 6.27 mmol, 1.0 eq.) in THF (30 ml) is added BH₃.Me₂S (0.9 ml, 9.4 mmol, 1.5 eq.) drop wise and the reaction mixture is heated at reflux for 2 h. The reaction mixture is then quenched with MeOH (0.5 ml) and then partitioned between water (30 ml) and ethyl acetate (100 ml). The organic layer is washed with brine (30 ml), dried over anhydrous Na₂SO₄ and evaporated to get the crude which is purified by column chromatography (silica gel; 4% ethyl acetate/hexanes) to yield the desired compound as a colourless oil. Yield: 43% (730 mg, 2.67 mmol).

2) Synthesis of the Acylated- & Sulfonylated Amino Acid Esters (B, C & D) General Method for Synthesis of the Amino Acid Esters (B, C & D)

Synthesis of the Acylated- & Sulfonylated Amino Acid Esters (B, C & D) Amino Acid Ester Overview:

No. Structure Amino acid ester (B, C & D) Comments B-01

3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid methyl ester (B-01) see below B-02

(3S)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid methyl ester (B-02) Yield: 95.2% Synthesis was carried out analogously to B-01^([a]) (2 equiv. of NEt₃) starting from A-02 HCl B-03

(3R)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid methyl ester (B-03) Yield: 93.1% Synthesis was carried out analogously to B-01^([a]) (2 equiv. of NEt₃) starting from A-03 HCl B-06

(8R)-8-[(2-chloro-benzoyl)amino]- 5,6,7,8-tetrahydro-naphthalene-2- carboxylic acid methyl ester (B-06) Yield: 96.3% synthesis was carried out analogously to B-01 starting from A-06 HCl B-07

(8S)-8-[(2-chloro-benzoyl)amino]- 5,6,7,8-tetrahydro-naphthalene-2- carboxylic acid methyl ester (B-07) Yield: >100% synthesis was carried out analogously to B-01 starting from A-07 HCl B-08

methyl 3-(2-chlorobenzamido)-2,2- dimethyl-2,3-dihydro-1H-indene-5- carboxylate (B-08) see below B-09

(R)-methyl 3-(2-methylbenzamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-09) see below B-10

(R)-methyl 3-(6-methoxy-2- naphthamido)-2,3-dihydro-1H- indene-5-carboxylate (B-10) see below B-11

(R)-methyl 4-(2- chlorobenzamido)chroman-6- carboxylate (B-11) Yield: 92% synthesis was carried out analogously to B-09 (reaction times were adapted) Starting from A-09 B-13

(R)-methyl 3-(2-chloro-4- methoxybenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-14) Yield: 80% synthesis was carried out analogously to B-10 starting from A-03 HCl B-14

(R)-methyl 3-(4-methoxy-2- methylbenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-14) Yield: 75% synthesis was carried out analogously to B-10 starting from A-03 HCl B-15

(R)-methyl 3-(2-chlorobenzamido)-6- fluoro-2,3-dihydro-1H-indene-5- carboxylate (B-15) see below B-17

(R)-methyl 4-(2-chlorobenzamido)-8- fluorochroman-6-carboxylate (B-17) Yield: 93% synthesis was carried out analogously to B-15 starting from A-13 B-18

(R)-methyl 3-(2-methyl-4- (trifluoromethoxy)benzamido)-2,3- dihydro-1H-indene-5-carboxylate (B- 18) Yield: 81% synthesis was carried out analogously to B-09 starting from A-03 HCl B-19

(R)-methyl 3-(2-chloro-6- (trifluoromethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylate (B- 19) Yield: >99% synthesis was carried out analogously to B-09 starting from A-03 HCl B-20

(R)-methyl 8-(2-chlorobenzamido)-3- fluoro-5,6,7,8-tetrahydronaphthalene- 2-carboxylate (B-20) Yield: 94% synthesis was carried out analogously to B-15 starting from A-14 B-21

(R)-methyl 3-(pyrimidine-5- carboxamido)-2,3-dihydro-1H- indene-5-carboxylate (B-21) Yield: 73% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl B-22

(R)-methyl 3-(2,3- dichlorobenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-22) Yield: 94% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl B-24

(R)-methyl 3-(2,5- dichlorobenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-24) Yield: 97% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl B-25

(R)-methyl 3-(2,6- dichlorobenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-25) Yield: 82% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl B-26

(R)-methyl 3-(2-fluorobenzamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-26) Yield: 83% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl B-27

(R)-methyl 3-(4-methoxy-2,5- dimethylbenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-27) Yield: 82% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl B-28

(R)-methyl 3-(2,6- dimethylbenzamido)-2,3-dihydro- indene-5-carboxylate (B-28) Yield: >99% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl B-29

(R)-methyl 4-(2-chlorobenzamido)-7- (trifluoromethyl)chroman-6- carboxylate (B-29) Yield: 50% synthesis was carried out analogously to B-15 (reaction times were adapted) starting from A-15 B-30

(R)-methyl 3-(2-chloro-6- fluorobenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-30) Yield: 96% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl B-31

(R)-methyl 3-(2-fluoro-6- (trifluoromethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylate (B- 31) Yield: 88% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl B-32

(R)-methyl 3-(2-methylnicotinamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-32) Yield: 82% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl B-33

(R)-methyl 3-(4- (trifluoromethyl)nicotinamido)-2,3- dihydro-1H-indene-5-carboxylate (B- 33) Yield: 79% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl B-39

methyl 3-(2-chlorobenzamido)-1,1- dimethyl-2,3-dihydro-1H-indene-5- carboxylate (B-39) 26% (reaction times were adapted) B-41

(R)-methyl 3-(2-chloro-N-(2,2,2- trifluoroethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylate (B- 41) see below B-42

(R)-methyl 3-(2-chloro-5- fluorobenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-42) Yield: 88% synthesis was carried out analogously to B-15 (reaction times were adapted) starting from A-03 HCl B-43

(R)-methyl 3-(3-methylbutanamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-43) Yield: 76% synthesis was carried out analogously to B-15 (reaction times were adapted) starting from A-03 HCl B-44

(3R)-methyl 3-(2-(2- chlorophenyl)propanamido)-2,3- dihydro-1H-indene-5-carboxylate (B- 44) Yield: 92% synthesis was carried out analogously to B-10 starting from A-03 HCl B-45

(R)-methyl 3-(2-(2-chlorophenyl)-2- methylpropanamido)-2,3-dihydro-1H- indene-5-carboxylate (B-45) Yield: 42% synthesis was carried out analogously to B-10 starting from A-03 HCl B-46

(R)-methyl 3-(1-(2- chlorophenyl)cyclopropanecarbox- amido)-2,3-dihydro-1H-indene-5- carboxylate (B-46) Yield: 76% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl B-47

(R)-methyl 3-(2-(2- chlorophenyl)acetamido)-2,3-dihydro- 1H-indene-5-carboxylate (B-47) Yield: 80% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl B-48

(R)-methyl 3-(2-(2- fluorophenyl)acetamido)-2,3-dihydro- 1H-indene-5-carboxylate (B-50) Yield: 74% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl B-49

(R)-methyl 3-(2-chloro-3- fluorobenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-49) Yield: 92% synthesis was carried out analogously to B-15 (reaction times were adapted) starting from A-03 HCl B-50

(R)-methyl 3-(2-o-tolylacetamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-50) Yield: 99% synthesis was carried out analogously to B-10 starting from A-03 HCl B-51

(S)-methyl 1-(2-chlorobenzamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-51) Yield: 49% synthesis was carried out analogously to B-15 starting from A-19 B-52

(S)-methyl 1-(2-chlorobenzamido)- 2,3-dihydro-1H-indene-4-carboxylate (B-52) Yield: 93% synthesis was carried out analogously to B-15 starting from A-21 B-53

(R)-methyl 1-(2-chlorobenzamido)- 2,3-dihydro-1H-indene-4-carboxylate (B-53) Yield: 90% synthesis was carried out analogously to B-15 starting from A-22 B-54

(R)-methyl 1-(2-chlorobenzamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-54) Yield: 83% synthesis was carried out analogously to B-15 starting from A-20 C-01

3-[[(4-methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-2,3-dihydro- 1H-indene-5-carboxylic acid methyl ester (C-01) see below C-02

(S)-methyl 8-(4-methoxy-2,6- dimethylphenylsulfonamido)-5,6,7,8- tetrahydronaphthalene-2-carboxylate (C-02) Yield: 77% Synthesis was carried out analogously to C-01^([a]) (2 equiv. of NEt₃) starting from A-07 C-03

(R)-methyl 8-(4-methoxy-2,6- dimethylphenylsulfonamido)-5,6,7,8- tetrahydronaphthalene-2-carboxylate (C-03) Yield: 95.6% Synthesis was carried out analogously to C-01^([a]) (2 equiv. of NEt₃) starting from A-06 C-04

(R)-methyl 3-(2- chlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 04) see below C-05

(R)-methyl 8-(2- chlorophenylsulfonamido)-5,6,7,8- tetrahydronaphthalene-2-carboxylate (C-05) Yield: 86% synthesis was carried out analogously to C-04 starting from A-06 HCl C-06

(R)-methyl 3-(2,3- dichlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 06) see below C-07

(R)-methyl 3-(2- fluorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 07) Yield: 96% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl C-08

(R)-methyl 3-(2- methylphenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 08) Yield: 97% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl C-09

(R)-methyl 3-(2- (trifluoromethyl)phenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylate (C-09) Yield: 68% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl C-10

(R)-methyl 3-(2,6- dichlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 10) Yield: 99% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl C-11

(R)-methyl 3-(2,5- dichlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 11) Yield: >99% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl C-12

(R)-methyl 3-(4-methoxy-2- (trifluoromethyl)phenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylate (C-12) Yield: 81% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl C-13

(R)-methyl 3-(4-methoxy-2- methylphenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 13) Yield: 93% synthesis was carried out analogously to C-06 starting from A-03 HCl C-14

(R)-methyl 3-(2-chloro-6- (trifluoromethyl)phenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylate (C-14) Yield: >99% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl C-15

(R)-methyl 3-((2- chlorophenyl)methylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylate (C-15) Yield: 88% synthesis was carried out analogously to C-06 starting from A-03 HCl C-16

(R)-methyl 3-(2-chloro-N- methylphenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 16) see below C-17

(S)-methyl 1-(2- chlorophenylsulfonamido)-2,3- dihydro-1H-indene-4-carboxylate (C- 17) Yield: 62% synthesis was carried out analogously to C-06 starting from A-21 C-18

(R)-methyl 1-(2- chlorophenylsulfonamido)-2,3- dihydro-1H-indene-4-carboxylate (C- 18) Yield: 68% synthesis was carried out analogously to C-06 starting from A-22 C-19

(R)-methyl 1-(2- chlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 19) Yield: 87% synthesis was carried out analogously to C-06 starting from A-20 D-01

3-(4-chloro-3-oxo-1,2-dihydro- isoindol-2-yl)-2,3-dihydro-1H-indene- 5-carboxylic acid methyl ester (D-01) see below D-02

(S)-methyl 8-(7-chloro-1- oxoisoindolin-2-yl)-5,6,7,8- tetrahydronaphthalene-2-carboxylate (D-02) see below D-03

®-methyl 8-(7-chloro-1-oxoisoindolin- 2-yl)-5,6,7,8-tetrahydronaphthalene- 2-carboxylate (D-03) Yield: 64.5% Synthesis was carried out analogously to D-02 starting from A-06 D-07

(R)-methyl 3-(7-chloro-1- oxoisoindolin-2-yl)-2,3-dihydro-1H- indene-5-carboxylate (G-07) see below D-08

(S)-methyl 1-(7-chloro-1- oxoisoindolin-2-yl)-2,3-dihydro-1H- indene-5-carboxylate (D-08) Yield: 48% synthesis was carried out analogously to D-07 starting from A-19 D-09

(R)-methyl 1-(7-chloro-1- oxoisoindolin-2-yl)-2,3-dihydro-1 indene-5-carboxylate (D-09) Yield: 89% synthesis was carried out analogously to D-07 starting from A-20 D-10

(R)-methyl 1-(7-chloro-1- oxoisoindolin-2-yl)-2,3-dihydro-1H- indene-4-carboxylate (D-10) Yield: 76% synthesis was carried out analogously to D-07 starting from A-22 D-11

(S)-methyl 1-(7-chloro-1- oxoisoindolin-2-yl)-2,3-dihydro-1H- indene-4-carboxylate (D-11) Yield: 56% synthesis was carried out analogously to D-07 starting from A-21 Notes: ^([a])Modified working up: The reaction mixture was finally diluted with methylene chloride, and sat. NaHCO₃ solution was added. The phases were separated and the aqueous phase was extracted 3× with methylene chloride. The organic phase was dried over Na₂SO₄ and concentrated. Concentration of the filtrate gave the crude product, which was purified by column chromatography over silica gel (hexane/ethyl acetate). General note: For reactions which were carried out in analogy to a described method, it may have been necessary to adapt the reaction conditions slightly, especially regarding the no. of equivalents of reagents employed, the interchangability of Et₃N and DIPEA, the reaction times (which were adjusted according to tlc results), the drying agent (magnesium sulfate or sodium sulfate) and the need for purification by column chromatography being required.

Synthesis of Amino Acid Ester B-01 3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (B-01)

Triethylamine (5.1 mmol) and 2-chloro-benzoyl chloride (1.2 equiv.) were added to an ice-cold solution of A-01 (1.71 mmol) in methylene chloride at 0° C. and under an inert atmosphere and the mixture was then stirred at room temperature for 1 h. The reaction mixture was finally diluted with methylene chloride and the organic phase was washed with water and sat. NaCl solution, dried over Na₂SO₄ and concentrated to obtain 3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (B-01). Yield: 93.5%

Synthesis of Amino Acid Ester B-08 Methyl 3-(2-chlorobenzamido)-2,2-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (B-08)

(I) Et₃N (1.6 ml) was added to a solution of methyl 3-amino-2,2-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (A-08) (6 g, crude) in abs. CH₂Cl₂ (20 ml) at 0° C. and the mixture was stirred for 10 min. 2-Chlorobenzoyl chloride (1.2 ml) was then added dropwise to the reaction mixture at the same temperature and the mixture was stirred for 3 h. The reaction mixture was diluted with CH₂Cl₂ (100 ml), washed with water (2×50 ml) and sat. NaCl solution (2×50 ml) and dried over sodium sulfate. The solvent was removed in vacuo and the crude material was purified by column chromatography (silica gel, 8% ethyl acetate in hexane) in order to obtain the desired product. Yield: 38% (after two steps)

Synthesis of Amino Acid Ester B-09 (R)-Methyl 3-(2-methylbenzamido)-2,3-dihydro-1H-indene-5-carboxylate (B-09)

N-Ethyl-diisopropylamine (2.5 eq.) and 2-methylbenzoyl chloride (1.2 equiv.) were added to an ice-cold solution of (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-03 HCl) (0.88 mmol, 1 equiv.) in methylene chloride at 0° C. under an inert atmosphere and the mixture was then stirred at room temperature for 2 d. The reaction mixture was diluted with ethyl acetate and the organic phase was washed with 10% NH₄Cl solution, sat. NaHCO₃ solution and sat. NaCl solution. The organic phase was dried over Na₂SO₄ and concentrated to obtain the crude product, which was purified by column chromatography (silica, cyclohexane/ethyl acetate 4:1). Yield: 70%

Synthesis of Amino Acid Ester B-10 (R)-Methyl 3-(6-methoxy-2-naphthamido)-2,3-dihydro-1H-indene-5-carboxylate (B-10)

N-Ethyl-diisopropylamine (3 eq.) was added to an ice-cold solution of 6-methoxy-2-naphthoic acid (1 eq.) in methylene chloride. The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-03 HCl) (0.989 mmol, 1 eq.) was added. The reaction mixture was then stirred at room temperature overnight. The mixture was diluted with ethyl acetate and the organic phase was washed with 10% NH₄Cl solution, sat. NaHCO₃ solution and sat. NaCl solution. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica, cyclohexane/ethyl acetate 2:1) to obtain the desired compound (B-10). Yield: 83%

Synthesis of Amino Acid Ester B-15 (R)-Methyl 3-(2-chlorobenzamido)-6-fluoro-2,3-dihydro-1H-indene-5-carboxylate (B-15)

Triethylamine (2.5 eq.) was added to a solution of (R)-methyl 3-amino-6-fluoro-2,3-dihydro-1H-indene-5-carboxylate hydrochloride (A-11) (0.773 mmol, 1 eq.) in methylene chloride (6 ml) at 00° C. and the mixture was stirred for 10 min. 2-Chlorobenzoyl chloride (1.2 eq.) was added dropwise to the reaction mixture at the same temperature and the mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with methylene chloride (50 ml) and was then washed with NH₄Cl solution (20 ml) and sat. NaCl solution (20 ml). The organic phase was dried over magnesium sulfate and the solvent was removed in vacuo. The crude material was purified by column chromatography (silica gel, ethyl acetate/cyclohexane 2:1) to yield the desired product (B-15). Yield: 97%

Synthesis of Amino Acid Ester B-41 (R)-methyl 3-(2-chloro-N-(2,2,2-trifluoroethyl)benzamido)-2,3-dihydro-1H-indene-5-carboxylate (B-41)

To a cooled (0° C.) solution of (R)-methyl 3-(2,2,2-trifluoroethylamino)-2,3-dihydro-1H-indene-5-carboxylate (A-18) (870 mg, 3.18 mmol, 1.0 eq.) in methylene chloride (12 ml) was added TEA (1.1 ml, 7.95 mmol, 2.5 eq.) and the reaction mixture was allowed to stir for 15 min. 2-Chlorobenzoyl chloride (0.44 ml, 3.50 mmol, 1.1 eq) was added to the reaction mixture and it was stirred at RT for 1 h. After completion of the reaction (monitored by TLC), the mixture was diluted with methylene chloride (50 ml) and the organic layer was washed with water (20 ml) and brine (20 ml), and dried over anhydrous Na₂SO₄. The solvent was evaporated to afford the crude product which was purified by column chromatography (silica gel; 7% ethyl acetate/hexanes) to yield the desired compounds as a colourless gummy solid. Yield: 85% (1.1 g, 2.67 mmol).

Synthesis of Amino Acid Ester C-01 3-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (C-01)

(I) Triethylamine (5.1 mmol) and 4-methoxy-2,6-dimethyl-benzenesulfonyl chloride (1.2 equiv.) were added to an ice-cold solution of A-01 (3.39 mmol) in methylene chloride at 0° C. and under an inert atmosphere and the mixture was then stirred at room temperature for 1 h. The reaction mixture was finally diluted with methylene chloride and the organic phase was washed with water and sat. NaCl solution, dried over Na₂SO₄ and concentrated to obtain 3-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (C-01). Yield: 50%

Synthesis of Amino Acid Ester C-04 (R)-Methyl 3-(2-chlorophenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate

Triethylamin (2.195 mmol, 2.5 eq.) and 2-chlorobenzene-1-sulfonyl chloride (0.878 mmol, 1 eq.) were added to an ice-cold solution of (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-03 HCl) (0.878 mmol, 1 eq.) in methylene chloride under an inert atmosphere. The mixture was then stirred at room temperature for 2 h. The reaction mixture was diluted with ethyl acetate (50 ml) and the organic phase was washed with 10% NH₄Cl solution (20 ml), sat. NaHCO₃ solution (20 ml) and sat. NaCl solution (20 ml). The organic phase was dried over MgSO₄ and concentrated in vacuo. The crude product was purified by column chromatography over silica gel (cyclohexane/ethyl acetate, 2:1) to obtain the desired product. Yield: >99%

Synthesis of Amino Acid Ester C-06 (R)-Methyl 3-(2,3-dichlorophenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate (C-06)

N-Ethyl-diisopropylamine (2.5 eq.) and 2,3-dichlorobenzene-1-sulfonyl chloride (1.2 eq.) were added to an ice-cold solution of (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-03 HCl) (0.88 mmol, 1 eq.) in methylene chloride at 0° C. under an inert atmosphere. The mixture was then stirred at room temperature for 3 h. The reaction mixture was diluted with ethyl acetate and the organic phase was washed with 10% NH₄Cl solution, sat. NaHCO₃ solution and sat. NaCl solution. The organic phase was dried over Na₂SO₄, filtered and concentrated. The crude product was purified by column chromatography (silica, cyclohexane/ethyl acetate, 2:1) to yield the desired compound (C-06). Yield: 97%

Synthesis of Amino Acid Ester C-16 (R)-Methyl 3-(2-chloro-N-methylphenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate (C-16)

TEA (864 μl, 6.23 mmol, 2.5 eq.) was added to a cooled (0° C.) solution of (R)-methyl 3-(methylamino)-2,3-dihydro-1H-indene-5-carboxylate (A-17) (2.49 mmol, 1.0 eq.) in methylene chloride (10 ml) and the reaction mixture was allowed to stir for 15 min. A solution of 2-chlorobenzene-1-sulfonyl chloride (407 μl, 2.99 mmol, 1.2 eq.) in methylene chloride (5 ml) was then added and the reaction mixture was stirred at RT for 4 h. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with methylene chloride (100 ml) and the organic layer was washed with water (50 ml) and brine (50 ml), and dried over anhydrous Na₂SO₄. The solvent was evaporated to afford the crude product which was purified by column chromatography (silica gel; 20% ethyl acetate/hexanes) to yield the desired compound as a white solid. Yield: 89% (840 mg, 2.216 mmol).

Synthesis of Amino Acid Ester D-01 3-(4-Chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (D-01)

(I) LiOH (50 mmol) was added to a solution of 2-chloro-6-methyl benzoic acid (1) (50 mmol) in THF (75 ml), the reaction mixture was stirred at 25° C. for 1 h, dimethyl sulfate (1.1 equiv.) was added and the mixture was heated under reflux for 16 h. The reaction mixture was then cooled to 0° C., 50 ml of an aqueous NH₄OH solution were added and the mixture was extracted with ethyl acetate. The organic phase was washed successively with water and sat. NaCl solution and dried over Na₂SO₄. Concentration of the organic phase gave the crude product (2), which was employed in the next step without further purification. Yield: 87%

(II) NBS (1.2 equiv.) and benzoyl peroxide (0.02 equiv.) were added to a suspension of 2-chloro-6-methyl benzoic acid methyl ester (2) (40 mmol) in CCl₄ and the mixture was heated under reflux for 16 h. The reaction mixture was cooled to room temperature and the solvent was concentrated under reduced pressure. The residue was taken up in chloroform and the mixture was filtered to remove the insoluble solid. Concentration of the filtrate gave the crude product (3), which was purified by column chromatography over aluminium oxide (hexane). Yield: 30%

Step 3: Triethylamine (1.2 equiv.) was added to a solution of 2-bromomethyl-6-chloro-benzoic acid methyl ester (3) (30 mmol) and 3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (A-01) (1 equiv.) in benzene (60 ml) and the reaction mixture obtained was heated under reflux for 25 h. The solvent was distilled off completely, the residue was taken up in methylene chloride and the mixture was washed successively with water and sat. NaCl solution and finally dried over Na₂SO₄. Concentration of the organic phase gave the crude product (D-01), which was purified by column chromatography (3:7 ethyl acetate in hexane). Yield: 50%

Synthesis of Amino Acid Ester D-02 (S)-Methyl 8-(7-chloro-1-oxoisoindolin-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate (D-02)

(I) (S)-Methyl 8-(7-chloro-1-oxoisoindolin-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate (A-07) (1 equiv.) was added to a solution of 2-bromomethyl-6-chlorobenzoic acid methyl ester (3) (0.83 mmol) in toluene (4.5 ml) and triethylamine (2.1 equiv.) and the reaction mixture obtained was heated under reflux for 16 h. Water and methylene chloride were added to the reaction mixture and the phases were separated. The aqueous phase was extracted 2× with methylene chloride. The organic phase was washed with sat. NaCl solution and finally dried over MgSO₄. Concentration of the organic phase gave the crude product (D-02), which was purified by column chromatography (ethyl acetate/hexane, 4:1). Yield: 67%

Synthesis of Amino Acid Ester D-07 (R)-Methyl 3-(7-chloro-1-oxoisoindolin-2-yl)-2,3-dihydro-1H-indene-5-carboxylate (D-07)

(3R)-3-Amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-03 HCl) (1.757 mmol, 1 equiv.) was added to a solution of 2-bromomethyl-6-chlorobenzoic acid methyl ester (1 equiv.) in toluene (5.4 ml) and triethylamine (2.1 equiv.). The resulting reaction mixture was heated at reflux for 16 h. Sat. NaHCO₃ solution (20 ml) and ethyl acetate (50 ml) were added to the mixture and the phases were separated. The organic phase was extracted with 0.05 N HCl solution and sat. NaCl solution and was then dried over MgSO₄. Concentration of the organic phase gave the crude product, which was purified by column chromatography (ethyl acetate/cyclohexane, 3:1) to yield the desired product (D-07). Yield: 72%

3) Synthesis of the Acylated- & Sulfonylated Amino Acids (E, F & G) General Method for Synthesis of the Amino Acid Esters (E, F & G)

Synthesis of the Acylated- & Sulfonylated Amino Acid Esters (E, F & G) Amino Acid Overview:

No. Structure Amino acid ester (E, F & G) Comments E-01

3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid(E-01) see below E-02

(3S)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid (E-02) Yield: 86.2% Synthesis was carried out analogously to E-07^([b]) (reaction times were adapted) starting from B-02 E-03

(3R)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid (E-03) Yield: 93.2% Synthesis was carried out analogously to E-07 (reaction times were adapted) starting from B-03 E-04

(3S)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-4-carboxylic acid (E 04) see below [from A-04] E-05

(3R)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-4-carboxylic acid (E 05) [from A-05] Yield: 54% Synthesis was carried out analogously to E-04 E-06

(8R)-8-[(2-chloro-benzoyl)amino]- 5,6,7,8-tetrahydro-naphthalene-2- carboxylic acid (E-06) see below E-07

(8S)-8-[(2-chloro-benzoyl)amino]- 5,6,7,8-tetrahydro-naphthalene-2- carboxylic acid (E-07) see below E-08

3-(2-chlorobenzamido)-2,2-dimethyl- 2,3-dihydro-1H-indene-5-carboxylic acid (E-08) see below E-09

(R)-3-(2-methylbenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-09) see below E-10

(R)-3-(6-methoxy-2-naphthamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-10) Yield: 80% Synthesis was carried out analogously to E-09 starting from B-10 E-11

(R)-4-(2-chlorobenzamido)chroman- 6-carboxylic acid (E-11) see below E-12

(R)-3-(2-chlorobenzamido)-6-methyl- 2,3-dihydro-1H-indene-5-carboxylic acid (E-12) see below E-13

(R)-3-(2-chloro-4- methoxybenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid (E-13) Yield: 97% Synthesis was carried out analogously to E-09 starting from B-13 E-14

(R)-3-(4-methoxy-2- methylbenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid (E-14) Yield: 86% Synthesis was carried out analogously to E-09 starting from B-14 E-15

(R)-3-(2-chlorobenzamido)-6-fluoro- 2,3-dihydro-1H-indene-5-carboxylic acid (E-15) Yield: >99% Synthesis was carried out analogously to E-11 starting from B-15 E-16

(R)-4-(2-chlorobenzamido)-7- fluorochroman-6-carboxylic acid (E- 16) Yield: 63% Synthesis was carried out analogously to E-12 Starting material available from NetChem. E-17

(R)-4-(2-chlorobenzamido)-8- fluorochroman-6-carboxylic acid (E- 17) Yield: 80% Synthesis was carried out analogously to E-11 starting from B-17 E-18

(R)-3-(2-methyl-4- (trifluoromethoxy)benzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-18) Yield: 95% Synthesis was carried out analogously to E-09 starting from B-18 E-19

(R)-3-(2-chloro-6- (trifluoromethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-19) Yield: 83% Synthesis was carried out analogously to E-09 starting from B-19 E-20

(R)-8-(2-chlorobenzamido)-3-fluoro- 5,6,7,8-tetrahydronaphthalene-2- carboxylic acid (E-20) Yield: 55% Synthesis was carried out analogously to E-11 starting from B-20 E-21

(R)-3-(pyrimidine-5-carboxamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-21) Yield: 79% Synthesis was carried out analogously to E-09 starting from B-21 E-22

(R)-3-(2,3-dichlorobenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-22) Yield: 88% Synthesis was carried out analogously to E-09 starting from B-22 E-24

(R)-3-(2,5-dichlorobenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-24) Yield: 47% Synthesis was carried out analogously to E-09 starting from B-24 E-25

(R)-3-(2,6-dichlorobenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-25) Yield: 90% Synthesis was carried out analogously to E-09 starting from B-25 E-26

(R)-3-(2-fluorobenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-26) Yield: 92% Synthesis was carried out analogously to E-09 starting from B-26 E-27

(R)-3-(4-methoxy-2,5- dimethylbenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid (E-27) Yield: 35% Synthesis was carried out analogously to E-09 starting from B-27 E-28

(R)-3-(2,6-dimethylbenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-28) Yield: 90% Synthesis was carried out analogously to E-09 starting from B-28 E-29

(R)-4-(2-chlorobenzamido)-7- (trifluoromethyl)chroman-6-carboxylic acid (E-29) Yield: 46% Synthesis was carried out analogously to E-09 starting from B-29 E-30

(R)-3-(2-chloro-6-fluorobenzamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-30) Yield: 84% Synthesis was carried out analogously to E-09 starting from B-30 E-31

(R)-3-(2-fluoro-6- (trifluoromethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-31) Yield: 79% Synthesis was carried out analogously to E-09 starting from B-31 E-32

(R)-3-(2-methylnicotinamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-32) Yield: 82% Synthesis was carried out analogously to E-09 starting from B-32 E-33

(R)-3-(4- (trifluoromethyl)nicotinamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-33) Yield: 35% Synthesis was carried out analogously to E-09 starting from B-33 E-39

3-(2-chlorobenzamido)-1,1-dimethyl- 2,3-dihydro-1H-indene-5-carboxylic acid (E-39) see below E-41

(R)-3-(2-chloro-N-(2,2,2- trifluoroethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-41) see below E-42

(R)-3-(2-chloro-5-fluorobenzamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-42) Yield: 84% Synthesis was carried out analogously to E-09 starting from B-42 E-43

(R)-3-(3-methylbutanamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-43) Yield: >99% Synthesis was carried out analogously to E-09 starting from B-43 E-44

(3R)-3-(2-(2- chlorophenyl)propanamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-44) Yield: 74% Synthesis was carried out analogously to E-09 starting from B-44 E-45

(R)-3-(2-(2-chlorophenyl)-2- methylpropanamido)-2,3-dihydro-1H- indene-5-carboxylic acid (E-45) Yield: 78% Synthesis was carried out analogously to E-09 starting from B-45 E-46

(R)-3-(1-(2- chlorophenyl)cyclopropanecarbox- amido)-2,3-dihydro-1H-indene-5- carboxylic acid (E-46) Yield: 66% Synthesis was carried out analogously to E-09 starting from B-46 E-47

(R)-3-(2-(2-chlorophenyl)acetamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-47) Yield: 67% Synthesis was carried out analogously to E-09 starting from B-47 E-48

(R)-3-(2-(2-fluorophenyl)acetamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-48) Yield: 91% Synthesis was carried out analogously to E-09 starting from B-48 E-49

(R)-3-(2-chloro-3-fluorobenzamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-49) Yield: 92% Synthesis was carried out analogously to E-09 starting from B-49 E-50

(R)-3-(2-o-tolylacetamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-50) Yield: 79% Synthesis was carried out analogously to E-09 starting from B-50 E-51

(S)-1-(2-chlorobenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-51) Yield: 96% Synthesis was carried out analogously to E-09 starting from B-51 E-52

(S)-1-(2-chlorobenzamido)-2,3- dihydro-1H-indene-4-carboxylic acid (E-52) Yield: 84% Synthesis was carried out analogously to E-09 starting from B-52 E-53

(R)-1-(2-chlorobenzamido)-2,3- dihydro-1H-indene-4-carboxylic acid (E-53) Yield: 84% Synthesis was carried out analogously to E-09 starting from B-53 E-54

(R)-1-(2-chlorobenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-54) Yield: 58% Synthesis was carried out analogously to E-09 starting from B-54 F-01

3-[[(4-methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-2,3-dihydro- 1H-indene-5-carboxylic acid (F-01) see below F-02

(S)-8-(4-methoxy-2,6- dimethylphenylsulfonamido)-5,6,7,8- tetrahydronaphthalene-2-carboxylic acid (F-02) Yield: 77.7% Synthesis was carried out analogously to F-01 starting from C-02 F-03

(R)-8-(4-methoxy-2,6- dimethylphenylsulfonamido)-5,6,7,8- tetrahydronaphthalene-2-carboxylic acid (F-03) see below F-04

(R)-3-(2-chlorophenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-04) Yield: 81% Synthesis was carried out analogously to E-09 starting from C-04 F-05

(R)-8-(2-chlorophenylsulfonamido)- 5,6,7,8-tetrahydronaphthalene-2- carboxylic acid (F-05) Yield: 60% Synthesis was carried out analogously to E-09 starting from C-05 F-06

(R)-3-(2,3- dichlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylic acid (F-06) see below F-07

(R)-3-(2-fluorophenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-07) Yield: 62% Synthesis was carried out analogously to F-06 starting from C-07 F-08

(R)-3-(2-methylphenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-08) Yield: 85% Synthesis was carried out analogously to F-06 starting from C-08 F-09

(R)-3-(2- (trifluoromethyl)phenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-09) Yield: 69% Synthesis was carried out analogously to F-06 starting from C-09 F-10

(R)-3-(2,6- dichlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylic acid (F-10) Yield: 68% Synthesis was carried out analogously to F-06 starting from C-10 F-11

(R)-3-(2,5- dichlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylic acid (F-11) Yield: 71% Synthesis was carried out analogously to F-06 (4 eq KOH) starting from C-11 F-12

(R)-3-(4-methoxy-2- (trifluoromethyl)phenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-12) Yield: 80% Synthesis was carried out analogously to F-06 starting from C-12 F-13

(R)-3-(4-methoxy-2- methylphenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylic acid (F-13) Yield: 77% Synthesis was carried out analogously to F-06 starting from C-13 F-14

(R)-3-(2-chloro-6- (trifluoromethyl)phenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-14) Yield: 34% Synthesis was carried out analogously to F-06 starting from C-14 F-15

(R)-3-((2- chlorophenyl)methylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-15) Yield: 64% Synthesis was carried out analogously to F-06 starting from C-15 F-16

(R)-3-(2-chloro-N- methylphenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylic acid (F-16) see below F-17

(S)-1-(2-chlorophenylsulfonamido)- 2,3-dihydro-1H-indene-4-carboxylic acid (F-17) Yield: 73% Synthesis was carried out analogously to F-06 starting from C-17 F-18

(R)-1-(2-chlorophenylsulfonamido)- 2,3-dihydro-1H-indene-4-carboxylic acid (F-18) Yield: 76% Synthesis was carried out analogously to F-06 starting from C-18 F-19

(R)-1-(2-chlorophenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-19) Yield: 62% Synthesis was carried out analogously to F-06 starting from C-19 G-01

3-(4-chloro-3-oxo-1,2-dihydro- isoindol-2-yl)-2,3-dihydro-1H-indene- 5-carboxylic acid (G-01) see below G-02

(S)-8-(7-chloro-1-oxoisoindolin-2-yl)- 5,6,7,8-tetrahydronaphthalene-2- carboxylic acid (G-02) Yield: 93.7% Synthesis was carried out analogously to G-01 starting from D-02 G-03

(R)-8-(7-chloro-1-oxoisoindolin-2-yl)- 5,6,7,8-tetrahydronaphthalene-2- carboxylic acid (G-03) Yield: 95.9% Synthesis was carried out analogously to G-01^([c]) starting from D-03 G-06

(R)-3-(5-methyl-3-oxo-1H-pyrrolo[1,2- c]imidazol-2(3H)-yl)-2,3-dihydro-1H- indene-5-carboxylic acid (G-06) see below G-07

(R)-3-(7-chloro-1-oxoisoindolin-2-yl)- 2,3-dihydro-1H-indene-5-carboxylic acid (G-07) Yield: 82% Synthesis was carried out analogously to E-09 starting from D-07 G-08

(S)-1-(7-chloro-1-oxoisoindolin-2-yl)- 2,3-dihydro-1H-indene-5-carboxylic acid (G-08) Yield: 87% Synthesis was carried out analogously to E-09 starting from D-08 G-09

(R)-1-(7-chloro-1-oxoisoindolin-2-yl)- 2,3-dihydro-1H-indene-5-carboxylic acid (G-09) Yield: 91% Synthesis was carried out analogously to E-09 starting from D-09 G-10

(R)-1-(7-chloro-1-oxoisoindolin-2-yl)- 2,3-dihydro-1H-indene-4-carboxylic acid (G-10) Yield: 86% Synthesis was carried out analogously to E-09 starting from D-10 G-11

(S)-1-(7-chloro-1-oxoisoindolin-2-yl)- 2,3-dihydro-1H-indene-4-carboxylic acid (G-11) Yield: 38% Synthesis was carried out analogously to E-09 starting from D-11 ^([b])Modified working up: Methanol was distilled off and the aqueous residue was diluted with diethyl ether and dist. water. The phases were separated and the aqueous phase was acidified with 1N HCl, during which a white solid precipitated out. This was filtered out with suction, washed with water and concentrated. ^([c])Modified working up: Methanol and THF were distilled off and the aqueous residue was diluted with diethyl ether and dist. water. The phases were separated and the aqueous phase was acidified with 1N HCl. Finally, the aqueous phase was extracted 4× with ethyl acetate (spot test) and the combined organic phases were dried over sodium sulfate and concentrated.

General note: For reactions which were carried out in analogy to a described method, it may have been necessary to adapt the reaction conditions slightly, especially regarding the no. of equivalents of reagents employed, the interchangability of Et₃N and DIPEA, the reaction times (which were adjusted according to tlc results), the drying agent (magnesium sulfate or sodium sulfate) and the need for purification by column chromatography being required.

Synthesis of Amino Acid E-01 3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (E-01)

(I) LiOH (5 equiv.) was added to a suspension of 3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (B-01) (11.75 mmol) in methanol (40 ml), tetrahydrofuran (40 ml) and water (30 ml) and the reaction mixture was stirred at 25° C. overnight. Methanol and THF were distilled off, the aqueous residue was acidified with 1 N HCl and the mixture was filtered. The white solid obtained was taken up in a mixture of 350 ml of acetone and 50 ml of methanol and the mixture was stirred for 1 h. After filtration, the white solid was dried in vacuo to obtain 3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (E-01). Yield: 75%

Synthesis of Amino Acid E-04 (S)-3-(2-Chlorobenzamido)-2,3-dihydro-1H-indene-4-carboxylic acid (E-04)

(I) N-Ethyl-diisopropylamine (2.5 mmol) and 2-chloro-benzoyl chloride (1.5 equiv.) were added to an ice-cold solution of A-04 (as corresponding HCl salt) (1.17 mmol) in ethanol at 0° C. and under an inert atmosphere and the mixture was then stirred at room temperature for 2 h. The ethanol was removed in vacuo and the residue was taken up in diethyl ether and water. The mixture was adjusted to pH 8-9 with dil. NaOH soln., the phases were separated and the aqueous phase was extracted 1× with diethyl ether. The aqueous phase was then adjusted to pH 2 with 1 N HCl and the phases were separated. The aqueous phase was extracted 2× with methylene chloride and the combined organic phases were dried over NaSO₄ and concentrated to obtain the amino acid (E-04). Yield: 92%

Synthesis of Amino Acid E-06 (8R)-8-[(2-Chloro-benzoyl)amino]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid (E-06)

LiOH (4 equiv.) was added to a suspension of (8R)-8-[(2-chloro-benzoyl)amino]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid methyl ester (B-06) in methanol and water and the reaction mixture was stirred at 25° C. for 2.5 hours. (According to TLC control: educt still present) The reaction mixture was topped up with 2 equiv. of LiOH and stirred at 25° C. overnight. Methanol was distilled off and the aqueous residue was diluted with ether and dist. water. The phases were separated and the aqueous phase was acidified with 1 N HCl. Finally, the aqueous phase was extracted 4× with ethyl acetate (spot test) and the extract was dried over sodium sulfate and concentrated. Yield: 81.4%.

Synthesis of Amino Acid E-07 (8S)-8-[(2-Chloro-benzoyl)amino]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid (E-07)

LiOH (6 equiv.) was added to a suspension of (8S)-8-[(2-chloro-benzoyl)amino]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid methyl ester (B-07) in methanol and water and the reaction mixture was stirred at 25° C. for 4 hours. (According to TLC control: educt still present). The reaction mixture was topped up with 1 equiv. of LiOH and stirred at 25° C. for 1 hour. Methanol was distilled off and the aqueous residue was diluted with ether and dist. water. The phases were separated and the aqueous phase was acidified with 1 N HCl. Finally, the aqueous phase was extracted 4× with ethyl acetate (spot test) and the extract was dried over sodium sulfate and concentrated. Yield: 84.8%

Synthesis of Amino Acid E-08 3-(2-Chlorobenzamido)-2,2-dimethyl-2,3-dihydro-1H-indene-5-carboxylic acid (E-08)

(I) A solution of LiOH.H₂O (4.0 eq.) in water (10 ml) was added to a solution of methyl 3-(2-chlorobenzamido)-2,2-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (B-08) (1.54 mmol, 1.0 eq.) in methanol (20 ml) and the mixture was then stirred at 25° C. for 5 h. When the reaction was complete (TLC control), the methanol was evaporated off in vacuo and the residual aqueous phase was diluted with water (50 ml) and washed with ethyl acetate (2×25 ml). The aqueous phase was acidified to pH=2-3 with 1 (N) HCl and the solid was filtered out. 2× toluene was added to the solid and the mixture concentrated again, in order to obtain the desired product solid. Yield: 90%

Synthesis of Amino Acid E-09 (R)-3-(2-Methylbenzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (E-09)

KOH (1 mol/l aq) (2 eq.) was added to a suspension of (R)-methyl 3-(2-methylbenzamido)-2,3-dihydro-1H-indene-5-carboxylate (B-09) (0.61 mmol, 1 eq.) in a mixture of ethanol (3.6 ml) and water (0.8 ml). The reaction mixture was stirred at room temperature overnight. Ethanol was removed in vacuo and the aqueous residue was diluted with diethyl ether and dist. water. The phases were separated and the aqueous phase was acidified with 1 N HCl to pH 3 and then extracted 4× with ethyl acetate. The combined organics were dried over sodium sulfate and concentrated in vacuo to yield the desired product (E-09). Yield: 88%

Synthesis of Amino Acid E-11 4-(2-Chlorobenzamido)-chroman-6-carboxylic acid (E-11)

KOH (1 mol/l aq) (2 eq.) was added to a suspension of methyl 4-(2-chlorobenzamido)chroman-6-carboxylate (B-11) (2.227 mmol, 1 eq.) in a mixture of ethanol (13 ml) and water (4.5 ml). The reaction mixture was stirred at room temperature for 16 h. Ethanol was removed in vacuo and the aqueous residue was diluted with diethyl ether (20 ml) and water (20 ml). The phases were separated and the aqueous phase was acidified with 1 N HCl to pH 3. The white precipitate was filtered out, washed with aqueous HCl solution and diethyl ether and finally dried in vacuo to obtain the desired product (E-11). Yield: 85%

Synthesis of Amino Acid E-12 (R)-3-(2-Chlorobenzamido)-6-methyl-2,3-dihydro-1H-indene-5-carboxylic acid (E-12)

Triethylamine (4.707 mmol, 1.5 eq.) was added to a solution of (R)-3-amino-6-methyl-2,3-dihydro-1H-indene-5-carboxylic acid hydrochloride (commercially available from NetChem) (1 eq., 3.138 mmol) in methylene chloride (16 ml) at 0° C. 2-Chlorobenzoyl chloride (1.2 eq.) was added dropwise to the reaction mixture at the same temperature and the mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with methylene chloride (50 ml), and washed with NH₄Cl solution (20 ml) and sat. NaCl solution (20 ml). The organic phase was dried over magnesium sulfate and the solvent was removed in vacuo. The crude material was purified by column chromatography (silica, ethyl acetate/cyclohexane 3:2) to yield the desired product (E-12). Yield: 43%

Synthesis of Amino Acid E-39 3-(2-Chlorobenzamido)-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylic acid (E-39)

Methyl 3-(2-chlorobenzamido)-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (B-39) (120 mg, 0.34 mmol, 1 eq.) was dissolved in a mixture of solvents THF:MeOH:H₂O (5:3:1, 5 ml) and LiOH (70 mg, 1.67 mmol, 5 eq.) was added portionwise at 0° C. The reaction mixture was stirred for 4 h and then the solvent was evaporated under reduced pressure. Water (4 ml) was added to the reaction to get a clear solution and it was then acidified with citric acid. This was followed by extraction with EtOAc (2×50 ml). The organic part was washed with brine (20 ml), dried over Na₂SO₄, filtered and evaporated under reduced pressure to yield the crude product which was purified by column chromatography (silica gel, 5% MeOH/MC) to yield the desired product as a white solid. Yield: 98% (115 mg, 0.34 mmol).

Synthesis of Amino Acid E-41 (R)-3-(2-chloro-N-(2,2,2-trifluoroethyl)benzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (E-41)

A solution of LiOH (153 mg, 3.64 mmol, 1.5 eq.) in water (8 ml) was added to a cooled (0° C.) solution of (R)-methyl 3-(2-chloro-N-(2,2,2-trifluoroethyl)benzamido)-2,3-dihydro-1H-indene-5-carboxylate (B-41) (1.0 g, 2.43 mmol, 1.0 eq.) in MeOH:THF (1:1, 16 ml) and the reaction mixture was then stirred at RT for 5 h. After completion of the reaction (monitored by TLC), the mixture was evaporated to dryness and diluted with water (15 ml). The aqueous layer was acidified to pH ˜3 using 1N HCl and then extracted with ethyl acetate (2×30 ml). The organic layer was washed with brine (20 ml), dried over anhydrous Na₂SO₄ and evaporated to afford the desired product as a white solid. Yield: 88% (850 mg, 2.14 mmol).

Synthesis of Amino Acid F-01 3-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (F-01)

(I) LiOH (5 equiv.) was added to a suspension of 3-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (C-01) (11.75 mmol) in methanol (40 ml), tetrahydrofuran (40 ml) and water (30 ml) and the reaction mixture was stirred at 25° C. overnight. Methanol and THF were distilled off, the aqueous residue was acidified with 1 N HCl and the mixture was filtered. The white solid obtained was taken up in a mixture of 350 ml of acetone and 50 ml of methanol and the mixture was stirred for 1 h. After filtration, the white solid was dried in vacuo to obtain 3-[[(4-methoxy-2,6-dimethyl-phenyl))sulfonyl]amino]-2,3-dihydro-1H-indene-5-carboxylic acid (F-01). Yield: 90%

Synthesis of Amino Acid F-03 (R)-8-(4-Methoxy-2,6-dimethylphenyl sulfonamido)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid (F-03)

(I) LiOH (6 equiv.) was added to a suspension of (R)-methyl 8-(4-methoxy-2,6-dimethylphenylsulfonamido)5,6,7,8-tetrahydronaphthalene-2-carboxylate (C-03) (1.115 mmol) in methanol and water and the reaction mixture was stirred at 25° C. overnight. The reaction mixture was topped up with 2 equiv. of LiOH and stirred at 25° C. for 1 h. The methanol was distilled off and the aqueous residue was diluted with diethyl ether and dist. water. The phases were separated and the aqueous phase was acidified with 1 N HCl. Finally, the aqueous phase was extracted 4× with ethyl acetate and the combined organic phases were dried over sodium sulfate and concentrated. Yield: 76%

Synthesis of Amino Acid F-06 (R)-3-(2,3-Dichlorophenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylic acid (F-06)

KOH (1 mol/l aq) (2 eq.) was added to a suspension of (R)-methyl 3-(2,3-dichlorophenyl-sulfonamido)-2,3-dihydro-1H-indene-5-carboxylate (C-06) (0.85 mmol, 1 eq.) in a mixture of ethanol (4.9 ml) and water (1.1 ml). The reaction mixture was stirred at room temperature overnight. Ethanol was removed in vacuo and the aqueous residue was diluted with diethyl ether and dist. water. The phases were separated and the aqueous phase was acidified to pH 3 with 1 N HCl and extracted 4× with ethyl acetate. The combined organics were dried over sodium sulfate and concentrated to obtain the desired product (F-06). Yield: 61%

Synthesis of Amino Acid F-16 (R)-3-(2-Chloro-N-methylphenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylicacid (F-16)

To a cooled (0° C.) solution of (R)-methyl 3-(2-chloro-N-methylphenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate (C-16) (840 mg, 2.216 mmol, 1.0 eq.) in MeOH:THF (1:1, 20 ml) was added dropwise a solution of LiOH.H₂O (185 mg, 4.433 mmol, 2.0 eq.) in water (10 ml) and the reaction mixture was stirred at RT for 3 h. After completion of the reaction (monitored by TLC), the reaction mixture was concentrated to dryness and diluted with water (20 ml) and washed with ethyl acetate (20 ml). The aqueous layer was acidified to pH=3 using 1N HCl and then extracted with methylene chloride (2×50 ml). The combined organic layers were dried over anhydrous Na₂SO₄ and concentrated to afford the desired product as an off-white solid. Yield: 58% (470 mg, 1.2876 mmol).

Synthesis of Amino Acid G-01 3-(4-Chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid (G-01)

(I) LiOH (5 equiv.) was added to a suspension of 3-(4-chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (D-01) (11.75 mmol) in methanol (90 ml) and water (30 ml) and the reaction mixture was stirred at 25° C. for 72 h. Methanol was distilled off, the aqueous residue was acidified with 1 N HCl and the mixture was filtered. The white solid obtained was taken up in a mixture of 350 ml of acetone and 50 ml of methanol and the mixture was stirred for 1 h. After filtration, the white solid was dried in vacuo to obtain 3-(4-chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid (G-01). Yield: 66%

Synthesis of Amino Acid G-06 (R)-3-(5-Methyl-3-oxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)-2,3-dihydro-1H-indene-5-carboxylic acid (G-06)

Step-1: tert-Butyl 2-formyl-5-methyl-1H-pyrrole-1-carboxylate

To a solution of 5-methyl-1H-pyrrole-2-carbaldehyde (500 mg, 4.58 mmol, 1 eq.) in acetonitrile (10 ml) were added DMAP (46 mg, 0.36 mmol, 1 eq.) and (Boc)₂O (1.19 g, 5.5 mmol, 1.2 eq.) and the mixture was stirred at RT for 2 h. The solvent was evaporated under reduced pressure and the crude product was purified by column chromatography (silica gel; 5% EtOAc/hexanes) to afford the desired product as a light yellow oil. Yield: 83% (800 mg, 3.8 mmol).

Step-2: (R)-tert-Butyl 2-((6-(methoxycarbonyl)-2,3-dihydro-1H-inden-1-ylamino)methyl)-1 H-pyrrole-1-carboxylate

A solution of (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (A-03) (361 mg, 1.88 mmol, 1 eq.) in methylene chloride (3 ml) was added to a solution of tert-butyl 2-formyl-5-methyl-1H-pyrrole-1-carboxylate (434 mg, 2.08 mmol, 1.1 eq.) in dry methylene chloride (17 ml) at 0° C. and the resulting reaction mixture was stirred at 25° C. for 2 h. The reaction mixture was cooled to 0° C. and then Na(OAc)₃BH (1.2 g, 5.66 mmol, 3 eq.) was added portionwise and it was stirred at 25° C. for 14 h. The reaction mixture was diluted with methylene chloride (200 ml) and washed with saturated sodium bicarbonate (50 ml), water (2×50 ml) and brine (50 ml), and dried over sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography (silica gel; 5% EtOAc/hexanes) to give the desired product as a light yellow oil. Yield: 82% (600 mg, 1.56 mmol).

Step-3: (R)-3-(5-Methyl-3-oxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)-2,3-dihydro-1H-indene-5-carboxylic acid

A solution of (R)-tert-butyl 2-((6-(methoxycarbonyl)-2,3-dihydro-1H-inden-1-ylamino)methyl)-1H-pyrrole-1-carboxylate (500 mg, 1.3 mmol, 1.0 eq.) in THF (5 ml) was added to a stirred suspension of NaH (104 mg, 2.6 mmol, 2.0 eq., 60% in mineral oil) in THF (15 ml) at 0° C. and the resulting reaction mixture was stirred at 25° C. for 14 h. The reaction mixture was quenched with water (50 ml) and washed with ethyl acetate (50 ml). The aqueous layer was acidified with 2 N HCl (5 ml) and extracted with ethyl acetate (2×100 ml). The combined organic fractions were washed with brine (50 ml), dried over sodium sulfate and the solvent evaporated under reduced pressure. The residue obtained was used for the next step without further purification. Yield: 26% (100 mg, 0.34 mmol).

Synthesis of the Amine Units Overview: Amine Units

AMN unit no. Structure AMN name AMN-01

9-pyridin-4-Yl-3,9-diazaspiro[5.5] undecane dihydrochloride (AMN-01) AMN-02

8-pyridin-4-Yl-3,8-diazaspiro[4.4]nonane dihydrochloride (AMN-02) AMN-03

8-pyridin-4-Yl-3,8-diazaspiro[4.5]decane dihydrochloride (AMN-03) AMN-04

9-(azetidin-1-Yl)-3-azaspiro[5.5]undecane dihydrochloride (AMN-04) AMN-05

9-(3,3-difluoro-azetidin-1-yl)-3- azaspiro[5.5]undecane dihydrochloride (AMN- 05) AMN-06

9-pyridin-4-Yloxy-3-azaspiro[5.5]undecane dihydrochloride (AMN-06) AMN-07

2-(pyridin-4-yl)-2,9-diazaspiro[5.5]undecane dihydrochloride (AMN-07) AMN-08

7-(pyridin-4-yl)-2,7-diazaspiro[3.5]nonane dihydrochloride (AMN-08) AMN-09

3-(1-methylpiperidin-4-yl)-3,9- diazaspiro[5.5]undecane Trihydrochlorid (AMN- 09) AMN-10

(4-methylpiperazin-1-yl)(3-azaspiro[5.5]undecan- 9-yl)methanone hydrochloride (AMN-10) AMN-12

3-((1-methylpiperidin-4-yl)methyl)-3,9- diazaspiro[5.5]undecane trihydrochloride (AMN- 12) AMN-13

1H-spiro[furo[3,4-c]pyridine-3,4′-piperidine] (AMN-13) AMN-14

2-(pyridin-4-yl)-2,8-diazaspiro[5.5]undecane trihydrochloride (AMN-14) AMN-15

7-(pyridin-4-yl)-2,7-diazaspiro[4.5]decane trihydrochloride (AMN-15) AMN-16

2-(pyridin-4-yl)-2,7-diazaspiro[4.5]decane trihydrochloride (AMN-16) AMN-17

9-(4-tert-butylpiperazin-1-yl)-3- azaspiro[5.5]undecane trihydrochloride (AMN- 17) AMN-18

pyrrolidin-1-yl(3-azaspiro[5.5]undecan-9- yl)methanone hydrochloride (AMN-18) AMN-19

2-(pyrrolidin-1-yl)-1-(2,8-diazaspiro[4.5]decan-8- yl)ethanone hydrochloride (AMN-19) AMN-20

8-(pyridin-2-yl)-2,8-diazaspiro[4.5]decane (AMN- 20) AMN-21

8-(4-chlorophenyl)-2,8-diazaspiro[4.5]decane (AMN-21) AMN-22

8-(4-fluorophenyl)-2,8-diazaspiro[4.5]decane (AMN-22) AMN-23

8-(4-(trifluoromethyl)phenyl)-2,8- diazaspiro[4.5]decane (AMN-23) AMN-24

8-(pyridin-3-yl)-2,8-diazaspiro[4.5]decane (AMN- 24) AMN-25

8-(pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane (AMN-25) AMN-26

8-(2-(trifluoromethyl)pyridin-4-yl)-2,8- diazaspiro[4.5]decane (AMN-26) AMN-27

4-(2,8-diazaspiro[4.5]decan-8-yl)-8- (trifluoromethyl)quinoline (AMN-27) AMN-28

8-(5-(trifluoromethyl)pyridin-2-yl)-2,8- diazaspiro[4.5]decane (AMN-28) AMN-29

6-(2,8-diazaspiro[4.5]decan-8-yl)isoquinoline trifluoroacetate (AMN-29) AMN-30

8-(2-(trifluoromethyl)pyrimidin-4-yl)-2,8- diazaspiro[4.5]decane trifluoroacetate (AMN-30) AMN-31

N-((R)-quinuclidin-3-yl)-3-azaspiro[5.5]undecane- 9-carboxamide hydrochloride (AMN-31) AMN-32

7-(3-azaspiro[5.5]undecan-9-yl)-5,6,7,8- tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine dihydrochloride (AMN-32) AMN-33

2-(pyridin-4-yl)-2,8-diazaspiro[4.5]decane dihydrochloride (AMN-33) AMN-34

N-((S)-quinuclidin-3-yl)-3-azaspiro[5.5]undecane- 9-carboxamide hydrochloride (AMN-34) AMN-35

(5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)- yl)(3-azaspiro[5.5]undecan-9-yl)methanone hydrochloride (AMN-35) AMN-36

8-(2,6-dimethylpyridin-4-yl)-2,8- diazaspiro[4.5]decane hydrochloride (AMN-36) AMN-37

8-(2-methylpyridin-4-yl)-2,8- diazaspiro[4.5]decane dihydrochloride (AMN-37) AMN-38

9-(2-(1H-imidazol-1-yl)ethoxy)-3- azaspiro[5.5]undecane (AMN-38) AMN-39

8-(pyridin-4-yl)-2-azaspiro[4.5]decan-8-ol (AMN- 39) AMN-41

8-(5-(trifluoromethyl)pyrimidin-2-yl)-2,8- diazaspiro[4.5]decane (AMN-41) AMN-42

9-(1H-imidazol-1-yl)-3-azaspiro[5.5]undecane (AMN-42) AMN-43

8-(pyridin-4-yl)-2-azaspiro[4.5]decane (AMN-43) AMN-44

8-(pyridin-3-yl)-2-azaspiro[4.5]decane (AMN-44) AMN-45

3-(pyridin-4-yl)-3,9-diazaspiro[5.6]dodecane (AMN-45) AMN-46

4-(2,8-diazaspiro[4.5]decan-8-yl)benzonitrile (AMN-46) AMN-47

8-(4-methoxyphenyl)-2,8-diazaspiro[4.5]decane (AMN-47)

Synthesis of the Amine Unit AMN-01 9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane dihydrochloride (AMN-01)

(i): tert-Butyl 3,9-diazaspiro[5.5]undecane-3-carboxylate (1 g, 3.931 mmol), 4-chloropyridinium chloride (1.765 g, 11.794 mmol) and triethylamine (2.2 ml, 15.725 mmol) were refluxed in 1-butanol (50 ml) for 15 h. Saturated sodium bicarbonate solution (30 ml) and ethyl acetate (80 ml) were added, the phases were separated and the aqueous phase was extracted with ethyl acetate (2×80 ml). The combined organic phases were dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel) with ethyl acetate/hexane/methanol/ammonia (25% aq.) 400/40/40/1.

Yield: 0.52 g, 39%

(ii): Hydrogen chloride in methanol (1.25 mol/l, 6.3 ml) was added to tert-butyl 9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecane-3-carboxylate (0.52 g, 1.569 mmol) and the mixture was refluxed for 1 h. The solvent was removed in vacuo, the residue was taken up in ethanol (3 ml) and the mixture was cooled. Acetone (80 ml) was added and the mixture was stirred in an ice bath for min. The precipitate was filtered out with suction, washed with diethyl ether and dried in vacuo. Yield: 0.4 g, 83%

Synthesis of the Amine Unit AMN-02 8-Pyridin-4-yl-3,8-diazaspiro[4.4]nonane dihydrochloride (AMN-02)

The synthesis was carried out analogously to the synthesis of amine AMN-01. For this, in step (i) tert-butyl 2,7-diazaspiro[4.4]nonane-2-carboxylate was reacted with 4-chloropyridinium chloride (yield: 50%). The Boc protective group was then split off in step (ii). When the reaction had ended and the methanol had been removed in vacuo, the residue was taken up in ethanol, the mixture was cooled and acetone was added. The resulting suspension was stirred in an ice bath for 30 min and the precipitate was filtered out with suction, washed with acetone and dried in vacuo. Yield (AMN-02): 73%

Synthesis of the Amine Unit AMN-03 8-Pyridin-4-yl-3,8-diazaspiro[4.5]decane dihydrochloride (AMN-03)

The synthesis was carried out analogously to the synthesis of amine AMN-01. For this, in step (i) tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate was reacted with 4-chloropyridinium chloride (yield: 22%). The Boc protective group was then split off in step (ii). When the reaction had ended and the methanol had been removed in vacuo, the residue taken up in ethanol, the mixture cooled and acetone added. The resulting suspension was stirred in an ice bath for 30 min and the precipitate was filtered out with suction, washed with acetone and dried in vacuo. Yield (AMN-03): 92%.

Synthesis of the Amine Unit AMN-04 9-(Azetidin-1-yl)-3-azaspiro[5.5]undecane dihydrochloride (AMN-04) Step (i): tert-Butyl 9-(azetidin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate

tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (step (iv) AMN-06) (1 g, 3.74 mmol) and azetidine (0.25 ml, 3.74 mmol) were initially introduced into 1,2-dichloroethane (15 ml), and sodium triacetoxyborohydride (1.1 g, 5.23 mmol) was added. The reaction mixture was stirred at room temperature for 3 d and saturated sodium bicarbonate solution was then added. After separation of the phases, the aqueous phase was extracted with methylene chloride (2×). The combined organic phases were washed with saturated sodium chloride solution (1×), dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate/methanol/ammonia (25% aq.) 100:10:1). Yield: 1 g (89%)

Step (ii): 9-(Azetidin-1-yl)-3-azaspiro[5.5]undecane dihydrochloride

Hydrogen chloride in methanol (1.25 mol/, 15.5 ml) was added to tert-butyl 9-(azetidin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate (1 g, 3.24 mmol) and the mixture was refluxed for 45 min. The solvent was removed in vacuo and the residue was dissolved in a small amount of ethanol. A solid was then precipitated out by addition of acetone, and finally diethyl ether was added and the precipitate formed was filtered out with suction. Yield: 0.87 g (95%)

Synthesis of the Amine Unit AMN-05 9-(3,3-Difluoro-azetidin-1-yl)-3-azaspiro[5.5]undecane dihydrochloride (AMN-05) Step (i): tert-Butyl 9-(3,3-difluoroazetidin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate

tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (step (iv) AMN-06) (1 g, 3.74 mmol) was added to 3,3-difluoroazetidine hydrochloride (0.484 g, 3.74 mmol) and triethylamine (0.52 ml, 3.74 mmol) in 1,2-dichloroethane (15 ml). The mixture was stirred for 5 min and sodium triacetoxyborohydride (1.1 g, 5.23 mmol) was then added and the mixture was stirred at room temperature for 3 d. Saturated sodium bicarbonate solution was added and closely separation of the phases the aqueous phase was extracted with methylene chloride (2×). The combined organic phases were washed with saturated sodium chloride solution (1×), dried over magnesium sulfate and concentrated in vacuo. Yield: 1.26 g (98%)

Step (ii): 9-(3,3-Difluoro-azetidin-1-yl)-3-azaspiro[5.5]undecane dihydrochloride

tert-Butyl 9-(3,3-difluoroazetidin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate (1.26 g, 3.66 mmol) was dissolved in hydrogen chloride in methanol (1.25 mol/l, 29 ml) and the solution was refluxed for 45 min. The solvent was removed in vacuo and the residue was dissolved in a small amount of ethanol. A solid was then precipitated out by addition of acetone. The mixture was stirred at room temperature for 10 min, diethyl ether was then added and the mixture was stirred at room temperature for a further 30 min. The precipitate formed was filtered out with suction, washed with diethyl ether and dried in vacuo. Yield: 1.1 g (95%)

Synthesis of the Amine Unit AMN-06 9-Pyridin-4-yloxy)-3-azaspiro[5.5]undecane dihydrochloride (AMN-06) Step (i): 1-(Benzyloxycarbonyl)piperidine-4-carboxylic acid

Water (75 ml) was added to piperidine-4-carboxylic acid (25 g) in THF (75 ml), followed by sodium bicarbonate (30.8 g). The mixture was cooled to 0° C. and Cbz chloride (38.9 ml) was added dropwise. The reaction mixture was then stirred at room temperature for 5 h (TLC control) When the reaction was complete, the organic solvent was distilled off and the residue was taken up in water (200 ml), and the mixture was washed with ethyl acetate (2×150 ml). The aqueous phase was acidified with dilute aqueous HCl solution and extracted with ethyl acetate. The organic phase was dried (Na₂SO₄) and concentrated in vacuo. Yield: 48.5 g (96%)

Step (ii): 1-Benzyl 4-methyl piperidine-1,4-dicarboxylate

1-(Benzyloxycarbonyl)piperidine-4-carboxylic acid (48.5 g) in methanol (485 ml) was cooled to 0° C. and thionyl chloride (13.34 ml) was added dropwise. The mixture was then refluxed for min (TLC control). When the reaction was complete, the methanol was distilled off, the residue was taken up in water (15 ml) and with ethyl acetate (2×150 ml). The combined organic phases were extracted with water and sat. sodium chloride solution and the extract was dried (Na₂SO₄) and concentrated in vacuo. Yield: 38 g (67%)

Step (iii): Benzyl 4-formylpiperidine-1-carboxylate

A solution of 1-benzyl 4-methyl piperidine-1,4-dicarboxylate (10 g) in toluene (100 ml) under nitrogen was cooled to −78° C. DIBAL-H (60.9 ml) was then added dropwise at −78° C. and the mixture was stirred at this temperature for 1 h (TLC control). Because the reaction was incomplete, a further 0.2 eq. of DIBAL-H was added and the mixture was stirred for a further min (TLC control: some educt and the corresponding alcohol were to be detected). Methanol (40 ml), followed by sat. sodium chloride solution (40 ml) were added slowly to the reaction mixture at −78° C. The mixture was filtered over Celite and the solvent was removed in vacuo. The residue was extracted with ethyl acetate (3×75 ml) and the extract was dried (Na₂SO₄) and concentrated in vacuo. The crude product obtained in this way was purified by column chromatography (silica gel, 20% ethyl acetate/hexane). Yield: 4.3 g (49%)

Step (iv): Benzyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate

Methyl vinyl ketone (1.64 ml), ethanol (5 ml) and water (5 ml) were added to benzyl 4-formylpiperidine-1-carboxylate (5 g). The mixture was then added to a boiling solution of potassium hydroxide (0.22 g) in ethanol (10 ml) and the resulting reaction mixture was refluxed for 1 h (TLC control). When the reaction was complete, the mixture was added to water (25 ml) and extracted with ethyl acetate (2×50 ml). The combined organic phases were dried (Na₂SO₄) and concentrated in vacuo. The crude product obtained in this way was purified by column chromatography (silica gel, 25% ethyl acetate/hexane). Yield: 2.8 g (46%)

Step (v): tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate

Boc anhydride (9.4 ml) and potassium carbonate (7.56 g) were added to benzyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate (8.2 g) in EtOH/water (9:1) (200 ml). Pd/C (1 g) was then added and hydrogenolysis was carried out under 80 psi for 4 h (TLC control). When the reaction was complete, the mixture was filtered over Celite and the residue was rinsed with ethanol and ethyl acetate. The filtrate was dried (Na₂SO₄) and concentrated in vacuo. The residue was taken up in ethyl acetate and water and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried (Na₂SO₄) and concentrated in vacuo. The crude product obtained in this way was purified by column chromatography (silica gel, 20% ethyl acetate/hexane). Yield: 2.92 g, 40%

Step (vi): tert-Butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate

tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (1.5 g) was dissolved in THF (7.5 ml) and the solution was cooled to −5° C. NaBH₄ (0.212 g) was then added and the mixture was stirred at room temperature for 1 h (TLC control). When the reaction was complete, acetic acid was added to the mixture and the methanol was then distilled off. The residue was taken up in water (50 ml) and the mixture was extracted with ethyl acetate (2×50 ml). The combined organic phases were dried (Na₂SO₄) and concentrated in vacuo. The crude product obtained in this way was purified by column chromatography (silica gel, 30% ethyl acetate/hexane). Yield: 1.2 g (80%)

Step (vii): tert-Butyl 9-(pyridin-4-yloxy)-3-azaspiro[5.5]undecane-3-carboxylate

4-Chloropyridine hydrochloride (1.3 g) was added to sodium hydride (0.89 g) in DMSO (20 ml) and the mixture was stirred for 10 min. tert-Butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate (2.0 g) in DMSO (20 ml) was then added slowly and the mixture was stirred overnight (TLC control: conversion approx. 30-35%). A catalytic amount of sodium iodide was added and the reaction mixture was stirred at 80° C. for 8 h (TLC control). Methanol and NaHCO₃ solution was added to the reaction mixture and the mixture was stirred for 20 min. It was then extracted with ethyl acetate and the extract was washed again with NaHCO₃ solution and cold water. The organic phase was dried (Na₂SO₄) and concentrated in vacuo. The crude product obtained in this way was purified by column chromatography (silica gel, 70% ethyl acetate/hexane). Yield: 1.0 g (40%)

Step (viii): 9-Pyridin-4-yloxy-3-azaspiro[5.5]undecane dihydrochloride

tert-Butyl 9-(pyridin-4-yloxy)-3-azaspiro[5.5]undecane-3-carboxylate (1 g, 2.886 mmol) was dissolved in methanol (2 ml), hydrogen chloride in methanol (1.25 mol/l, 11.5 ml) was added and the mixture was refluxed for 30 min. The solvent was removed in vacuo and the residue was dissolved in a small amount of ethanol. Acetone (approx. 25 ml) was subsequently added, the mixture was stirred at 0° C. for 30 min and the solid formed was finally filtered out with suction. Yield: 0.96 g (>99%)

Synthesis of the Amine Unit AMN-07 2-(Pyridin-4-yl)-2,9-diazaspiro[5.5]undecane dihydrochloride (AMN-07) Step (i): tert-Butyl 2-(pyridin-4-yl)-2,9-diazaspiro[5.5]undecane-9-carboxylate

tert-Butyl 2,9-diazaspiro[5.5]undecane-9-carboxylate (1 g, 3.931 mmol), 4-chloropyridinium chloride (1.765 g, 11.794 mmol) and N-ethyl-diisopropylamine (2.7 ml, 15.724 mmol) were refluxed in 2-propanol (8 ml) for 15 h, saturated NaHCO₃ solution (20 ml) and ethyl acetate (8 ml) were added, the phases were separated and the aqueous phase was extracted with ethyl acetate (2×80 ml). The combined organic phases were dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica; ethyl acetate/methanol/ammonia (25% aq.) 100:10:0.25). Yield: 0.67 g (51.4%)

Step (ii): 2-(Pyridin-4-yl)-2,9-diazaspiro[5.5]undecane dihydrochloride

Hydrogen chloride in methanol (1.25 mol/, 15.9 ml) was added to tert-butyl 2-(pyridin-4-yl)-2,9-diazaspiro[5.5]undecane-9-carboxylate (0.66 g, 1.991 mmol) and the mixture was refluxed for 2 h. The solvent was removed in vacuo, the residue was taken up in ethanol (5 ml) and the mixture was cooled. Acetone (20 ml) was added and the mixture was stirred at 0° C. for 30 min. Diethyl ether (50 ml) was added and the precipitate was filtered out with suction, washed with diethyl ether and dried in vacuo. Yield: 0.42 g (69%)

Synthesis of the Amine Unit AMN-08 7-(Pyridin-4-yl)-2,7-diazaspiro[3.5]nonane dihydrochloride (AMN-08)

The synthesis was carried out analogously to the synthesis of amine AMN-07. For this, in step (i) tert-butyl 2,7-diazaspiro[3.5]nonane-2-carboxylate was reacted with 4-chloropyridinium chloride and in step (ii) the Boc protective group was split off in order to obtain the amine AMN-08.

Synthesis of the Amine Unit AMN-09 3-(1-Methylpiperidin-4-yl)-3,9-diazaspiro[5.5]undecane trihydrochloride (AMN-09)

The synthesis was carried out analogously to the synthesis of amine AMN-04. For this, in step (i) tert-butyl 3.9-diazaspiro[5.5]undecane-3-carboxylate was reacted with 1-methylpiperidin-4-one and in step (ii) the Boc protective group was split off in order to obtain the amine AMN-08.

Synthesis of the Amine Unit AMN-10 (4-Methylpiperazin-1-yl)(3-azaspiro[5.5]undecan-9-yl)methanone hydrochloride (AMN-10) Step (i): tert-Butyl 9-(4-methylpiperazine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carboxylate

O-(1H-Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (0.32 g, 1 eq.) and 1-hydroxybenzotriazole hydrate (0.14 g, 1 eq.) were added to a solution of 3-(tert-butoxycarbonyl)-3-azaspiro[5.5]undecane-9-carboxylic acid (commercially obtainable from Anthem, Order No. A1106) (0.3 g, 1 eq.) in tetrahydrofuran (20 ml) and the reaction mixture was stirred at room temperature for 0.5 h. 1-Methylpiperazine (0.11 ml, 1 eq.) and N-ethyl-diisopropylamine (0.17 ml, 1 eq.) were then added and the mixture was stirred at room temperature overnight. For working up, the reaction mixture was concentrated, methylene chloride and sat. NaHCO₃ solution were added to the residue and the aqueous phase was extracted with methylene chloride a further 2×. The combined organic phases were washed 1 x with sat. NaCl solution, dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (silica; ethyl acetate/ethanol/ammonia (25% aq.) 10:1:0.05) in order to obtain the desired product (AMN-10). Yield: 0.22 g (101%)

Step (ii): (4-Methylpiperazin-1-yl)(3-azaspiro[5.5]undecan-9-yl)methanone hydrochloride

Ethanol (3 ml) and acetyl chloride (0.24 ml, 3.43 mmol) were added to tert-butyl 9-(4-methylpiperazine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carboxylate (0.26 g, 0.685 mmol) and the mixture was stirred at room temperature for 12 h. When the reaction was complete, the solvent was removed in vacuo. Yield: 0.22 g (101%)

Synthesis of the Amine Unit AMN-12 3-((1-Methylpiperidin-4-yl)methyl)-3,9-diazaspiro[5.5]undecane trihydrochloride (AMN-12)

The synthesis was carried out analogously to the synthesis of amine AMN-05. For this, in step (i) tert-butyl 3.9-diazaspiro[5.5]undecane-3-carboxylate was reacted with 1-methylpiperidine-4-carbaldehyde and in step (ii) the Boc protective group was split off in order to obtain the amine AMN-12.

Amine Unit AMN-13 1H-Spiro[furo[3,4-c]pyridine-3,4′-piperidine](AMN-13)

The amine AMN-13 is commercially obtainable from Shanghai AOK Chem group (Order No. A3031).

Synthesis of the Amine Unit AMN-14 2-(Pyridin-4-yl)-2,8-diazaspiro[5.5]undecane trihydrochloride (AMN-14)

The synthesis was carried out analogously to the synthesis of amine AMN-07. For this, in step (i) tert-butyl 2,8-diazaspiro[5.5]undecane-2-carboxylate was reacted with 4-chloropyridinium chloride (yield: 66%). The Boc protective group was then split off. In step (ii), ethanol (8 ml) and acetyl chloride (0.45 ml, 6.335 mmol) were added to tert-butyl 8-(pyridin-4-yl)-2,8-diazaspiro[5.5]undecane-2-carboxylate (0.42 g, 1.267 mmol) and the mixture was stirred at room temperature for 12 h. When the reaction was complete, the solvent was removed in vacuo. Yield: 0.39 g (90%)

Synthesis of the Amine Unit AMN-15 7-(Pyridin-4-yl)-2,7-diazaspiro[4.5]decane trihydrochloride (AMN-15)

The synthesis was carried out analogously to the synthesis of amine AMN-07.

For this, in step (i) tert-butyl 2,7-diazaspiro[4.5]decane-2-carboxylate was reacted with 4-chloropyridinium chloride (yield: 53%). The Boc protective group was then split off. In step (ii), ethanol (8 ml) and acetyl chloride (0.37 ml, 5.355 mmol) were added to tert-butyl 7-(pyridin-4-yl)-2,7-diazaspiro[4.5]decane-2-carboxylate (0.34 g, 1.071 mmol) and the mixture was stirred at room temperature for 12 h. When the reaction was complete, the solvent was removed in vacuo. Yield: 0.28 g (80%)

Synthesis of the Amine Unit AMN-16 2-(Pyridin-4-yl)-2,7-diazaspiro[4.5]decane trihydrochloride (AMN-16)

The synthesis was carried out analogously to the synthesis of amine AMN-07. For this, in step (i) tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate was reacted with 4-chloropyridinium chloride (yield: 41%). The Boc protective group was then split off. In step (ii), ethanol (6 ml) and acetyl chloride (0.27 ml, 3.94 mmol) were added to tert-butyl 2-(pyridin-4-yl)-2,7-diazaspiro[4.5]decane-7-carboxylate (0.25 g, 0.788 mmol) and the mixture was stirred at room temperature for 12 h. When the reaction was complete, the solvent was removed in vacuo. Yield: 0.23 g (89%).

Synthesis of the Amine Unit AMN-17 9-(4-tert-Butylpiperazin-1-yl)-3-azaspiro[5.5]undecane trihydrochloride (AMN-17) Step (i): tert-Butyl 9-(4-tert-butylpiperazin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate

1-tert-Butylpiperazine (0.21 g, 1.49 mmol) was added to tert-butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (see product of step (v) of the synthesis of amine AMN-06) (0.4 g, 1.49 mmol) and triethylamine (0.52 ml, 3.74 mmol) in methylene chloride (9.6 ml). The mixture was stirred for 5 min and sodium triacetoxyborohydride (0.44 g, 2.09 mmol) was then added and the mixture was stirred at room temperature overnight. Sat. NaHCO₃ solution was added and, after separation of the phases, the organic phase was washed with sat. NaCl solution (2×), dried over sodium sulfate and concentrated in vacuo. Yield: 0.27 g (45%)

Step (ii): 9-(4-tert-Butylpiperazin-1-yl)-3-azaspiro[5.5]undecane trihydrochloride

Hydrogen chloride in methanol (1.25 mol/l, 5.3 ml) was added to tert-butyl 9-(4-tert-butylpiperazin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate (0.26 g, 0.661 mmol) and the mixture was refluxed for 1 h. The solvent was removed in vacuo, the residue was taken up in ethanol (10 ml) and the mixture was stirred for 15 min. Diethyl ether (50 ml) was added and the mixture was then stirred at room temperature. The precipitate was filtered out with suction, washed with diethyl ether and dried in vacuo. Yield: 0.23 g (86%)

Synthesis of the Amine Unit AMN-18 Pyrrolidin-1-yl(3-azaspiro[5.5]undecan-9-yl)methanone hydrochloride (AMN-18) Step (i): tert-Butyl 9-(pyrrolidine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carboxylate

N-Ethyl-diisopropylamine (4 eq.) was added to a solution of 3-(tert-butoxycarbonyl)-3-azaspiro[5.5]undecane-9-carboxylic acid (commercially obtainable from Anthem, Order No. A1106) (0.35 g, 1.18 mmol, 1 eq.) in methylene chloride. The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before the amine (1.1 eq.) was finally added. The reaction mixture was then stirred at room temperature overnight. For working up, the reaction mixture was washed in each case 1× with 10% strength NH₄Cl solution, sat. NaHCO₃ solution and sat. NaCl solution. The organic phase was dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (silica; ethyl acetate/ethanol) in order to obtain the desired product. Yield: 0.23 g (56%)

Step (ii): Pyrrolidin-1-yl(3-azaspiro[5.5]undecan-9-yl)methanone hydrochloride

Ethanol (4 ml) and acetyl chloride (0.23 ml, 0.66 mmol) were added to tert-butyl 9-(pyrrolidine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carboxylate (0.25 g, 0.788 mmol) and the mixture was stirred at room temperature for 12 h. When the reaction was complete, the solvent was removed in vacuo. Yield: 0.18 g (96%)

Synthesis of the Amine Unit AMN-19 2-(Pyrrolidin-1-yl)-1-(2,8-diazaspiro[4.5]decan-8-yl)ethanone hydrochloride (AMN-19)

The synthesis was carried out analogously to the synthesis of amine AMN-18. For this, in step (i) tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate was reacted with 2-(pyrrolidin-1-yl)acetic acid and in step (ii) the Boc protective group was split off in order to obtain the amine AMN-19.

Synthesis of the Amine Unit AMN-20 8-(Pyridin-2-yl)-2,8-diazaspiro[4.5]decane (AMN-20) Step 1: tert-Butyl 8-(pyridin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate

Sodium t-butylate (5.4 mmol, 3.0 eq.) was added to a stirred mixture of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (1.8 mmol, 1.0 eq.) and 2-bromopyridine (1.8 mmol, 1.0 eq.) in toluene (30 ml) and the reaction mixture was degassed with N₂ for 15-20 min. BINAP (0.108 mmol, 0.06 eq.) and Pd(OAc)₂ (0.036 mmol, 0.02 eq.) were added and the reaction mixture obtained is heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 30% ethyl acetate in hexane). Yield: 69%

Step 2: 8-(Pyridin-2-yl)-2,8-diazaspiro[4.5]decane

TFA (1 ml) was added to a solution of tert-butyl 8-(pyridin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.47 mmol, 1.0 eq.) in methylene chloride (3 ml) at 0° C. and the reaction mixture was stirred at 25° C. for 1 h. When the reaction was complete (TLC), the solvent was removed in vacuo in order to obtain the desired amine (AMN-20).

Synthesis of the Amine Unit AMN-21 8-(4-Chlorophenyl)-2,8-diazaspiro[4.5]decane (AMN-21) Step 1: tert-Butyl 8-(4-chlorophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate

Sodium t-butylate (4.99 mmol, 3.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (1.66 mmol, 1.0 eq.) and 1-chloro-4-iodobenzene (1.66 mmol, 1.0 eq.) in toluene (12 ml) and the reaction mixture was degassed with N₂. BINAP (0.099 mmol, 0.06 eq.) and Pd(OAc)₂ (0.03 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 10% ethyl acetate in hexane), so that the desired product was achieved. Yield: 50%

Step 2: tert-Butyl 8-(4-chlorophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate

TFA (1 ml) was added to a solution of tert-butyl 8-(4-chlorophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.47 mmol, 1.0 eq.) in methylene chloride (3 ml) at 0° C. and the reaction mixture was stirred at 25° C. for 1 h. When the reaction was complete, the solvent was removed in vacuo in order to obtain the desired amine (AMN-21).

Synthesis of the Amine Unit AMN-22 8-(4-Fluorophenyl)-2,8-diazaspiro[4.5]decane (AMN-22) Step 1: tert-Butyl 8-(4-fluorophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate

Sodium t-butylate (6.24 mmol, 3.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.08 mmol, 1.0 eq.) and 1-bromo-4-fluorobenzene (2.08 mmol, 1.0 eq.) in toluene (15 ml) and the reaction mixture was degassed with N₂. BINAP (0.12 mmol, 0.06 eq.) and Pd(OAc)₂ (0.04 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 12% ethyl acetate in hexane), so that the desired product was achieved. Yield: 28%

Step 2: 8-(4-Fluorophenyl)-2,8-diazaspiro[4.5]decane

TFA (0.6 ml) was added to a cooled (0° C.) solution of tert-butyl 8-(4-fluorophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.31 mmol, 1.0 eq.) in methylene chloride (2 ml) and the reaction mixture was stirred at 25° C. for 1 h. When the reaction was complete, the solvent was removed in vacuo in order to obtain the desired amine (AMN-22).

Synthesis of the Amine Unit AMN-23 8-(4-(Trifluoromethyl)phenyl)-2,8-diazaspiro[4.5]decane (AMN-23) Step 1: tert-Butyl 8-(4-(trifluoromethyl)phenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate

Sodium t-butylate (6.24 mmol, 3.0 eq.) was added to a stirred mixture of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.08 mmol, 1.0 eq.) and 1-bromo-4-(trifluoromethyl)benzene (2.08 mmol, 1.0 eq.) in toluene (15 ml) and the reaction mixture was degassed with N₂. BINAP (0.12 mmol, 0.06 eq.) and Pd(OAc)₂ (0.04 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 10% ethyl acetate in hexane), so that the desired product was achieved. Yield: 37%

Step 2: 8-(4-(Trifluoromethyl)phenyl)-2,8-diazaspiro[4.5]decane

TFA (1 ml) was added to a cooled (0° C.) solution of tert-butyl 8-(4-(trifluoromethyl)phenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.47 mmol, 1.0 eq.) in methylene chloride (3 ml) and the reaction mixture was stirred at 25° C. for 1 h. When the reaction was complete, the solvent was removed in vacuo in order to obtain the desired amine (AMN-23).

Synthesis of the Amine Unit AMN-24 8-(Pyridin-3-yl)-2,8-diazaspiro[4.5]decane (AMN-24) Step 1: tert-Butyl 8-(pyridin-3-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate

Sodium t-butylate (5.4 mmol, 3.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (1.8 mmol, 1.0 eq.) and 3-bromopyridine (1.8 mmol, 1.0 eq.) in toluene (30 ml) and the reaction mixture was degassed with N₂. BINAP (0.108 mmol, 0.06 eq.) and Pd(OAc)₂ (0.036 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo. The crude product was purified by column chromatography (silica gel, 30% ethyl acetate in hexane) in order to obtain the desired product. Yield: 69%

Step 2: 8-(Pyridin-3-yl)-2,8-diazaspiro[4.5]decane

TFA (2 ml) was added to a solution of tert-butyl 8-(pyridine-3-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (1.14 mmol, 1.0 eq.) in methylene chloride (6 ml) at 0° C. and the reaction mixture was stirred at 25° C. for 2 h. When the reaction was complete, the solvent was concentrated in vacuo in order to obtain the desired amine (AMN-24).

Synthesis of the Amine Unit AMN-25 8-(Pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane (AMN-25) Step 1: tert-Butyl 8-(pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate

A stirred mixture of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (0.2 mmol, 1 eq.), 2-chloropyrimidine (0.4 mmol, 2 eq.), DIPEA (2 eq.), DMA (2 eq.) in 1,4-dioxane (0.5 ml) was subjected to microwave radiation in a 10 ml pressure tube at 120° C. for 30 min. After concentration, the crude product was purified by column chromatography (silica gel, 20% ethyl acetate in hexane) in order to obtain the desired product. Yield: 51%

Step 2: 8-(Pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane

TFA (1 ml) is added to a solution of tert-butyl 8-(pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.53 mmol, 1.0 eq.) in methylene chloride (5 ml) at 0° C. and the reaction mixture is stirred at 25° C. for 1 h. When the reaction was complete, the solvent was removed in vacuo in order to obtain the desired amine (AMN-25).

Synthesis of the Amine Unit AMN-26 8-(2-(Trifluoromethyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decane (AMN-26) Step 1: tert-Butyl 8-(2-(trifluoromethyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate

Sodium t-Butylate (6.24 mmol, 3.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.08 mmol, 1.0 eq.) and 4-bromo-2-(trifluoromethyl)pyridine (2.08 mmol, 1.0 eq.) in toluene (15 ml) and the reaction mixture was then degassed with N₂. BINAP (0.12 mmol, 0.06 eq.) and Pd(OAc)₂ (0.04 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 2% methanol in methylene chloride), in order to obtain the desired product. Yield: 62%

Step 2: 8-(2-(Trifluoromethyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decane

TFA (1.5 ml) is added to a solution of tert-butyl 8-(2-(trifluoromethyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.64 mmol, 1.0 eq.) in methylene chloride (5 ml) at 0° C. and the reaction mixture is stirred at 25° C. for 1 h. When the reaction was complete, the solvent was removed in vacuo in order to obtain the desired amine (AMN-26).

Synthesis of the Amine Unit AMN-27 4-(2,8-Diazaspiro[4.5]decan-8-yl)-8-(trifluoromethyl)quinoline (AMN-27) Step 1: tert-Butyl 8-(8-(trifluoromethyl)quinolin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate

A mixture of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.5 mmol, 1.0 eq.) and 4-bromo-8-(trifluoromethyl)quinoline (2.5 mmol, 1.0 eq.) and ^(t)BuONa (7.5 mmol, 3.0 eq.) in toluene (12 ml) was degassed with argon for 10 min. BINAP (0.15 mmol, 0.06 eq.) and Pd(OAc)₂ (0.05 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated under reflux for 14 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 22-25% ethyl acetate in hexane), in order to obtain the desired product. Yield: 40%

Step 2: 4-(2,8-Diazaspiro[4.5]decan-8-yl)-8-(trifluoromethyl)quinoline

TFA (1 ml) was added to a cooled (0° C.) solution of tert-butyl 8-(8-(trifluoromethyl)quinolin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.69 mmol, 1.0 eq.) in methylene chloride (4 ml) and the reaction mixture was stirred at 25° C. for 2 h. When the reaction was complete, the solvent was removed in vacuo in order to obtain the desired amine (AMN-27).

Synthesis of the Amine Unit AMN-28 8-(5-(Trifluoromethyl)pyridin-2-yl)-2,8-diazaspiro[4.5]decane (A-28) Step 1: tert-Butyl 8-(5-(trifluoromethyl)pyridin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate

A mixture of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.5 mmol, 1.0 eq.) and 2-bromo-5-(trifluoromethyl)pyridine (2.5 mmol, 1.0 eq.) and ^(t)BuONa (7.5 mmol, 3.0 eq.) in toluene (12 ml) was degassed with argon for 10 min. BINAP (0.15 mmol, 0.06 eq.) and Pd(OAc)₂ (0.05 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated under reflux for 14 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 22-25% ethyl acetate in hexane), in order to obtain the desired product. Yield: 40%

Step 2: 8-(5-(Trifluoromethyl)pyridin-2-yl)-2,8-diazaspiro[4.5]decane

TFA (1 ml) was added to a cooled (0° C.) solution of tert-butyl 8-(5-(trifluoromethyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.69 mmol, 1.0 eq.) in methylene chloride (4 ml) and the reaction mixture was stirred at 25° C. for 2 h. When the reaction was complete, the solvent was concentrated in vacuo in order to obtain the desired amine (AMN-28) solid.

Synthesis of the Amine Unit AMN-29 6-(2,8-Diazaspiro[4.5]decan-8-yl)isoquinoline trifluoroacetate (A-29) Step 1: tert-Butyl 8-(isoquinolin-6-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate

Sodium t-butylate (6.24 mmol, 3.0 eq.) was added to a solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.08 mmol, 1.0 eq.) and 6-bromoisoquinoline (2.08 mmol, 1.0 eq.) in toluene (10 ml) and the reaction mixture was degassed with N₂. BINAP (0.124 mmol, 0.06 eq.) and Pd acetate (0.04 mmol, 0.02 eq.) were added and the mixture was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated on a rotary evaporator. The crude product was purified by means of column chromatography (silica gel, 5% methanol in methylene chloride) in order to obtain the desired product. Yield: 52%

Step 2: 6-(2,8-Diazaspiro[4.5]decan-8-yl)isoquinoline trifluoroacetate

TFA (2 ml) was added to a cooled (0° C.) solution of tert-butyl 8-(isoquinolin-6-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.544 mmol, 1.0 eq.) in methylene chloride (10 ml) and the reaction mixture was stirred at room temperature for 1 h. When the reaction was complete, the solvent was removed on a rotary evaporator. The crude product was employed directly in the next step.

Synthesis of the Amine Unit AMN-30 8-(2-(Trifluoromethyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane trifluoroacetate (A-30) Step 1: 4-Chloro-2-(trifluoromethyl)pyrimidine

N,N-Dimethylaniline (6.06 mmol. 2.3 eq.) was added dropwise to a stirring solution of 2-(trifluoromethyl)pyrimidin-4-ol (2.72 mmol, 1 eq.) in POCl₃ (4 ml) and the reaction mixture was stirred at 110° C. for 2 h. The reaction mixture was concentrated and the brown liquid was diluted with cold water (50 ml) and rendered basic with saturated sodium carbonate solution (50 ml). The mixture was extracted with methylene chloride (3×100 ml) and the combined organic phases were washed with water (2×50 ml) and sat. NaCl solution (50 ml) and dried over sodium sulfate. After concentration on a rotary evaporator, a blue liquid remained, which was employed in the next step without purification.

Step 2: tert-Butyl 8-(2-(trifluoromethyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate

4-Chloro-2-(trifluoromethyl)pyrimidine (2.72 mmol, 1 eq.) and isopropanol (4 ml) were introduced into a microwave vessel. tert-Butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.72 mmol, 1 eq.) and DIPEA (0.6 ml, 6.8 mmol), 2.5 eq.) were added in succession and the reaction mixture was introduced into a microwave oven at 75° C. for 45 min. After TLC control, the reaction mixture was concentrated on a rotary evaporator. A reddish liquid remained and was diluted with methylene chloride (200 ml). The organic phase was washed with water (2×100 ml) and sat. NaCl solution (50 ml), dried over sodium sulfate and concentrated. The brown liquid residue was purified by column chromatography (silica gel, ethyl acetate). Yield: 47%

Step 3: 8-(2-(Trifluoromethyl)pyridimin-4-yl)-2,8-diazaspiro[4.5]decane trifluoroacetate

TFA (3.19 ml, 41.45 mmol) was added to a cooled (0° C.) solution of tert-butyl 8-(2-(trifluoromethyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (400 mg, 1.03 mmol, 1.0 eq.) in methylene chloride (15 ml) and the reaction mixture was stirred at room temperature for 1 h. When the reaction was complete, the solvent was removed on a rotary evaporator. The crude product was employed directly in the next step. Crude weight: 570 mg

Synthesis of the Amine Unit AMN-31 N—((R)-Quinuclidin-3-yl)-3-azaspiro[5.5]undecane-9-carboxamide hydrochloride (AMN-31) Step 1: tert-Butyl 9-((R)-quinuclidin-3-ylcarbamoyl)-3-azaspiro[5.5]undecane-3-carboxylate

N-Ethyl-diisopropylamine (4 eq.) was added to an ice-cold solution of 3-(tert-butoxycarbonyl)-3-azospiro[5.5]undecane-9-carboxylic acid (1.009 mmol, 1 eq.) in methylene chloride. The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before (R)-quinuclidin-3-amine dihydrochloride (1.1 eq.) was finally added. The reaction mixture was stirred at room temperature overnight. The mixture was diluted with ethyl acetate and the organic phase was washed with 10% NH₄Cl solution, sat. NaHCO₃ solution and sat. NaCl solution. The organic phase was dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (silica, ethyl acetate/ethanol/ammonia (25% aq) 100:10:1) to obtain the desired product. Yield: 27%

Step 2: N—((R)-Quinuclidin-3-yl)-3-azaspiro[5.5]undecane-9-carboxamide hydrochloride (AMN-31)

Acetyl chloride (5 eq.) was added to an ice-cold solution of 9-((R)-quinuclidin-3-ylcarbamoyl)-3-azaspiro[5.5]undecane-3-carboxylate (0.271 mmol, 1 eq.) in ethanol. The reaction mixture was stirred at room temperature overnight. The solvent was removed in vacuo and the residue dissolved in acetone/ethanol (1:3, 3 ml) and diethyl ether (20 ml) was added. The white solid was filtered out, washed with diethyl ether and dried in vacuo. Yield: 86%

Synthesis of the Amine Unit AMN-32 7-(3-Azaspiro[5.5]undecan-9-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine dihydrochloride (AMN-32) Step 1: tert-Butyl 9-(5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl)-3-azaspiro[5.5]undecane-3-carboxylate

Acetic acid (2.34 eq.) was added to a solution of tert-butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (1.122 mmol, 1 eq.) and 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine (1.14 eq.) in methylene chloride (7 ml). Sodium triacetoxyborhydride (1.4 eq) was then added and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with methylene chloride and sat. NaHCO₃ solution. The aqueous phase was washed with methylene chloride (2×20 ml), and the combined organic phases were dried over Na₂SO₄ and concentrated in vacuo. The crude product was purified by column chromatography (silica, ethyl acetate/ethanol 10:1) to obtain the desired product. Yield: 62%

Step 2: 7-(3-Azaspiro[5.5]undecan-9-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine dihydrochloride (AMN-32)

Acetyl chloride (5 eq.) was added to an ice-cold solution of tert-butyl 9-(5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl)-3-azaspiro[5.5]undecane-3-carboxylate (0.666 mmol, 1 eq.) in ethanol (5 ml). The reaction mixture was stirred at room temperature for overnight. The white solid was filtered out, washed with diethyl ether and dried in vacuo. Yield: 91%

Synthesis of the Amine Unit AMN-33 2-(Pyridin-4-yl)-2,8-diazaspiro[4.5]decane dihydrochloride (AMN-33) Step 1: tert-Butyl 2-(pyridin-4-yl)-2,8-diazaspiro[4.5]decane-8-carboxylate

A mixture of tert-butyl 2,8-diazaspiro[4.5]decane-8-carboxylate (10.402 mmol, 1.0 eq.), N-ethyl-diisopropylamine (4.0 eq.) and 4-chloropyridine hydrochloride (3.0 eq.) in 2-propanol (20 ml) was stirred at 90° C. overnight. Ethyl acetate and sat. NaHCO₃ solution were added and the aqueous phase was extracted with ethyl acetate a further 4×. The combined organic phases were washed 1× with sat. NaCl solution, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica, ethyl acetate/ethanol/ammonia (25% aq) 500:100:2). Yield: 45%

Step 2: 2-(Pyridin-4-yl)-2,8-diazaspiro[4.5]decane dihydrochloride (AMN-33)

Acetyl chloride (5 eq.) was added to an ice-cold solution of tert-butyl 2-(pyridin-4-yl)-2,8-diazaspiro[4.5]decane-8-carboxylate (3.78 mmol, 1 eq.) in ethanol (14 ml). The reaction mixture was stirred at room temperature overnight. The solvent was concentrated in vacuo and the residue was dissolved in ethanol/acetone (2:1, 30 ml). The white solid which precipitated was filtered out, washed with diethyl ether and dried in vacuo. Yield: 98%

Synthesis of the Amine Unit AMN-34 N—((S)-Quinuclidin-3-yl)-3-azaspiro[5.5]undecane-9-carboxamide hydrochloride (AMN-34)

Synthesis of this amine was carried out in analogy to Amine AMN-31 employing (S)-quinuclidin-3-amine dihydrochloride as the amine starting material. Step 1—yield: 54%; Step 2—yield: 81%

Synthesis of the Amine Unit AMN-35 (5,6-Dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl)(3-azaspiro[5.5]undecan-9-yl)methanone hydrochloride (AMN-35)

Synthesis of this amine was carried out in analogy to Amine AMN-31 employing 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine as the amine starting material. Step 1—yield: 69%; Step 2—yield: 93%

Synthesis of the Amine Unit AMN-36 8-(2,6-Dimethylpyridin-4-yl)-2,8-diazaspiro[4.5]decane hydrochloride (AMN-36)

Synthesis of this amine was carried out in analogy to Amine AMN-33 employing tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (1 eq.) and 4-chloro-2-methylpyridine (3 eq.) as starting materials. In step 1 the number of equivalents of N-ethyl-diisopropylamine was adjusted to 3. Step 1—yield: 50%; Step 2—yield: 68%

Synthesis of the Amine Unit AMN-37 8-(2-Methylpyridin-4-yl)-2,8-diazaspiro[4.5]decane dihydrochloride (AMN-37)

Synthesis of this amine was carried out in analogy to Amine AMN-33 employing tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (1 eq.) and 4-chloro-2-methylpyridine (5 eq.) as starting materials. In step 1 the number of equivalents of N-ethyl-diisopropylamine was adjusted to 5 and the reaction mixture was stirred at 90° C. for 48 h. Step 1—yield: 87%; Step 2—yield: >99%

Synthesis of the Amine Unit AMN-38 9-(2-(1H-Imidazol-1-yl)ethoxy)-3-azaspiro[5.5]undecane (AMN-38) Step 1: 1-tert-Butyl 4-ethyl piperidine-1,4-dicarboxylate

Di-tert-butyldicarbonate (95.39 mmol, 1.5 eq.) was added to a stirred solution of ethyl piperidine-4-carboxylate (63.7 mmol, 1.0 eq.) and Et₃N (127.40 mmol, 2.0 eq.) in MC (200 ml) at 0° C. The mixture was then stirred at 25° C. for 16 h. It was diluted with MC (100 ml) and washed with water (100 ml) and brine (100 ml). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to give the desired product which was employed in the next step without further purification. Yield: 93%

Step-2: tert-Butyl 4-(hydroxymethyl)piperidine-1-carboxylate

A solution of 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate (60.0 mmol, 1.0 eq.) in dry THF (80 ml) was added dropwise to a suspension of LAH (90.0 mmol, 1.5 eq.) in THF (120 ml) at 0° C. After addition of the reagent was completed the reaction mixture was stirred at 25° C. for 1 h. The reaction mixture was quenched by very slow addition of a mixture of THF-water (9:1, 36 ml) and 10% NaOH solution (7.2 ml). The mixture was then filtered through celite and filtrate was concentrated to yield the desired product as a white solid which was used in the next step without further purification. Yield: 77%

Step-3: tert-Butyl 4-formylpiperidine-1-carboxylate

A mixture of dry DMSO (223.26 mmol, 4.0 eq.) and dry methylene chloride (100 ml) was added dropwise to a solution of oxalyl chloride (111.63 mmol, 2.0 eq.) in dry methylene chloride (100 ml) at −78° C. A solution of tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate (55.81 mmol, 1.0 eq.) in dry methylene chloride (100 ml) was added dropwise to the reaction mixture at same temperature and it was then stirred for 30 min. Et₃N (279.07 mmol, 5.0 eq.) was added at −78° C. and the reaction mixture allowed to slowly warm to 25° C. and stir for another 30 min. The reaction mixture was quenched with saturated ammonium chloride solution (200 ml), diluted with methylene chloride (100 ml) and the layers were separated. The organic layer was washed with brine (200 ml) and dried over sodium sulfate. The solvent was evaporated under reduced pressure to give the crude desired product as light orange oil which is used in the next step without purification. Yield: 95%

Step-4: tert-Butyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate

3 N KOH in ethanol (7.5 ml) was added to mixture of tert-butyl 4-formylpiperidine-1-carboxylate (60.0 mmol, 1.0 eq.) and methyl vinyl ketone (70.0 mmol, 1.3 eq.) in THF (100 ml) at 0° C. and the mixture was then stirred at 25° C. for 16 h. The solvent was evaporated under reduced pressure and the residue diluted with water (100 ml) and KHSO₄ solution at 0° C. The aqueous layer was extracted with MC (2×150 ml). The combined organic layers were washed with brine (100 ml) and dried over sodium sulfate. The solvent was evaporated under reduced pressure and the crude product was purified by silica gel column chromatography eluting with 10-12% ethyl acetate in hexanes to give the desired product as a light brown sticky solid. Yield: 25%

Step-5: tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate

A solution of tert-butyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate (15.09 mmol, 1.0 eq.) in MeOH (40 ml) was degassed with argon for 15 min and then Pd—C (1.0 g) was added. The reaction mixture was stirred under H₂ balloon pressure at 25° C. for 16 h. The mixture was filtered through celite and filtrate concentrated to give the desired product as a light yellow sticky solid. Yield: >99%

Step-6: tert-Butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate

NaBH₄ (56.18 mmol, 3.0 eq.) was added portionwise to a stirred solution of tert-butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (18.72 mmol, 1.0 eq.) in MeOH (40 ml) at 00° C. and the resulting reaction mixture was stirred at 25° C. for 1 h. The solvent was evaporated under reduced pressure. The residue was dissolved in MC (100 ml) and washed with water (50 ml) and brine (50 ml). the organic layer was dried over sodium sulfate and concentrated under reduced pressure to give the crude product which was used in the next step without further purification. Yield: 95%

Step-7: tert-Butyl 9-(allyloxy)-3-azaspiro[5.5]undecane-3-carboxylate

KOH (257.46 mmol, 21.0 eq.), allyl bromide (36.8 mmol, 3.0 eq.) and 18-crown-6 (4.9 mmol, 0.4 eq.) were added to a solution of tert-butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate (12.26 mmol, 1.0 eq.) in toluene (65 ml) at 0° C. and then reaction mixture was heated at reflux for 1 h. Then the reaction mixture was diluted with ethyl acetate (150 ml) and washed with water (150 ml) and brine (150 ml). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to yield the crude product which was purified by silica gel column chromatography eluting with 10% ethyl acetate in hexanes to afford the desired product as a yellow oil. Yield: 92%

Step-8: tert-Butyl 9-(2-oxoethoxy)-3-azaspiro[5.5]undecane-3-carboxylate

O₃ gas was passed through a stirred solution of tert-butyl 9-(allyloxy)-3-azaspiro[5.5]undecane-3-carboxylate (6.47 mmol, 1.0 eq.) in MeOH (40 ml) for 45 min at −78° C. Dimethylsulfide (77.64 mmol, 12.0 eq.) was added dropwise to the reaction mixture at 0° C. and it was stirred for 30 min at 25° C. The reaction mixture was concentrated under reduced pressure to yield the crude product as a light yellow oil which was used in next step without further purification. Yield: 99%

Step-9: tert-Butyl 9-(2-hydroxyethoxy)-3-azaspiro[5.5]undecane-3-carboxylate

NaBH₄ (13.46 mmol, 2.0 eq.) was added portion wise to a stirred solution of tert-butyl 9-(2-oxoethoxy)-3-azaspiro[5.5]undecane-3-carboxylate (6.73 mmol, 1.0 eq.) in MeOH (65 ml) at 00° C. and the resulting reaction mixture was stirred at 25° C. for 16 h. The solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (300 ml) and washed with water (200 ml) and brine (200 ml). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography eluting with 20% ethyl acetate in hexanes to give the desired product as a yellow sticky solid. Yield: 40%

Step-10: tert-Butyl 9-(2-(methylsulfonyloxy)ethoxy)-3-azaspiro[5.5]undecane-3-carboxylate

Methanesulfonyl chloride (5.43 mmol, 2.0 eq.) was added dropwise to a stirred solution of tert-butyl 9-(2-hydroxyethoxy)-3-azaspiro[5.5]undecane-3-carboxylate (2.71 mmol, 1.0 eq.) and Et₃N (9.485 mmol, 3.5 eq.) in MC (30 ml) at 0° C. and the resulting reaction mixture was stirred at 25° C. for 3 h. The reaction mixture was diluted with MC (150 ml), washed with water (100 ml) and brine (100 ml) and dried over sodium sulfate. The solvent was evaporated under reduce pressure to give the crude product as a yellow sticky solid which was used in the next step reaction without further purification. Yield: 99%

Step-11: tert-butyl 9-(2-(1H-imidazol-1-yl)ethoxy)-3-azaspiro[5.5]undecane-3-carboxylate

A solution of tert-butyl 9-(2-(methylsulfonyloxy)ethoxy)-3-azaspiro[5.5]undecane-3-carboxylate (2.68 mmol, 1.0 eq.) in DMF (10 ml) was added dropwise to a stirred mixture of NaH (8.04 mmol, 3.0 eq.) and imidazole (5.36 mmol, 2.0 eq.) in DMF (15 ml) at 0° C. and the resulting mixture was stirred at 25° C. for 16 h. The reaction mixture was diluted with ethyl acetate (300 ml) and washed with water (200 ml) and brine (200 ml). The organic layer was dried over sodium sulfate and concentrated under reduce pressure to give the crude product which was purified by silica gel column chromatography eluting with 2% MeOH in MC to afford the desired product as a yellow oil. Yield: 84%

Step-12: 9-(2-(1H-Imidazol-1-yl)ethoxy)-3-azaspiro[5.5]undecane (AMN-38)

TFA (6.25 ml) was added to a solution of tert-butyl 9-(2-(1H-imidazol-1-yl)ethoxy)-3-azaspiro[5.5]undecane-3-carboxylate (2.28 mmol, 1.0 eq.) in MC (25 ml) at 0° C. and the mixture was stirred at 25° C. for 2 h. The reaction mixture was concentrated under reduced pressure and the residue was azeotroped with MC to give the crude product which was used in the next step without further purification.

Synthesis of the Amine Unit AMN-39 8-(Pyridin-4-yl)-2-azaspiro[4.5]decan-8-ol (AMN-39)

Step-1: Ethyl 2-(1,4-dioxaspiro[4.5]decan-8-ylidene)acetate

A solution of compound 1 (10.05 g, 64.04 mmol, 1.0 eq.) in THF (30 ml) was added dropwise to a suspension NaH (1.84 g, 76.85 mmol, 1.2 eq.) in THF (90 ml) at 0° C. and the mixture was stirred at same temperature for 1 h. Triethyl phosphonoacetate (16.5 ml, 83.25 mmol, 1.3 eq.) was added to the reaction mixture at −20° C. and the reaction mixture was allowed to warm to RT and stir for 2 h. The reaction mixture was diluted with ethyl acetate (100 ml), washed with water (2×100 ml) and the organic layer dried over sodium sulfate. The solvent was evaporated under reduced pressure to obtain the crude product which was purified by column chromatography (silica gel; 5% ethyl acetate/hexanes) to yield compound 2. Yield: 94% (17.28 g, 60.2 mmol).

Step-2: Ethyl 2-(8-(nitromethyl)-1,4-dioxaspiro[4.5]decan-8-yl)acetate

Nitromethane (5.665 g, 98.81 mmol, 1.5 eq.) was added to a solution of compound 2 (14.0 g, 61.87 mmol, 1.0 eq.) in dry THF (68 ml) at RT followed by addition of a 1M solution of TBAF (68 ml, 68.07 mmol, 1.1 eq.) in THF, which was added dropwise at the same temperature. The reaction mixture was heated to reflux for 20 h. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with water (100 ml) and extracted with diethyl ether (3×100 ml). The combined organic layers were washed with sat. KHSO₄ solution (2×100 ml) and dried over sodium sulfate. The solvent was evaporated under reduced pressure to obtain the crude product which was purified by column chromatography (silica gel; 5-15% ethyl acetate/hexanes) to yield compound 3. Yield: 65% (11.5 g, 40.07 mmol).

Step-3: 1,4-Dioxa-10-azadispiro[4.2.4̂{8}.2̂{5}]tetradecan-11-one

A solution of compound 3 (11.5 g, 40.07 mmol, 1.0 eq.) in EtOH (200 ml) was degassed with argon for 20 min followed by addition of Raney nickel (10.0 g). The reaction mixture was stirred under H₂ balloon pressure for 2 d. After completion of the reaction (monitored by TLC), the mixture was filtered through celite and the filtrate was concentrated to give the crude product which was purified by column chromatography (silica gel; 30% ethyl acetate/hexanes) to yield compound 4. Yield: 70% (5.9 g, 27.96 mmol).

Step-4: 10-Benzyl-1,4-dioxa-10-azadispiro[4.2.4̂{8}.2̂{5}]tetradecan-11-one

NaH 60% in mineral oil (1.67 g, 41.63 mmol, 1.2 eq.) was added portionwise to a stirred solution of compound 4 (7.37 g, 34.88 mmol, 1.0 eq.) in THF (150 ml) at 0° C. and the reaction mixture was stirred at RT for 30 min. Benzyl bromide (7.16 g, 41.86 mmol, 1.2 eq.) was then added dropwise to the reaction mixture at 0° C. and the mixture was stirred at RT for 18 h. The reaction mixture was diluted with water (100 ml) and ethyl acetate (200 ml) and the layers were separated. The organic layer was washed with brine (2×100 ml) and dried over sodium sulfate. The solvent was evaporated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 10-15% ethyl acetate/hexanes) to yield compound 5. Yield: 76% (8.0 g, 26.58 mmol).

Step-5: 10-Benzyl-1,4-dioxa-10-azadispiro[4.2.4̂{8}.2̂{5}]tetradecane

A solution of compound 5 (12.0 g, 39.8 mmol, 1.0 eq.) in dry THF (200 ml) was added dropwise to a stirred suspension of LAH (2.27 g, 59.8 mmol, 1.5 eq.) in THF (200 ml) at 0° C. and reaction mixture is stirred at RT for 5 h. The reaction mixture was quenched with THF: H₂O (9:1, 30 ml) and 15% NaOH (2.5 ml) with cooling and stirred at RT for 1 h. Reaction mixture is filtered through celite and filtrate is concentrated under reduced pressure to get desired compound 6 which was used in the next step without further purification. Yield: 91% (10.40 g, 36.24 mmol).

Step-6: 2-Benzyl-2-azaspiro[4.5]decan-8-one

2N HCl (15 ml) was added to a solution of compound 6 (10.4 g, 36.24 mmol, 1.0) in MeOH (350 ml) and the mixture was stirred at RT for 24 h. After completion of the reaction (monitored by LCMS), the solvent was evaporated under reduced pressure. The residue was dissolved in water (200 ml), basified with sat. NaHCO₃ solution and extracted with ethyl acetate (2×500 ml). The organic layer was dried over sodium sulfate and evaporated to give the crude product which was purified by column chromatography (silica gel; 2% MeOH/MC) to yield compound 7. Yield: 85% (7.48 g, 30.78 mmol).

Step-7: 2-Benzyl-8-(pyridin-4-yl)-2-azaspiro[4.5]decan-8-ol

A solution of 4-bromopyridine.HCl (1.8 g, 9.25 mmol, 1.25 eq.) in dry THF (20 ml) was added dropwise to a solution of n-BuLi (7.4 ml, 14.8 mmol, 2.0 eq., 2M solution in hexane) in THF (10 ml) at −78° C. and the reaction mixture was stirred at same temperature for 1 h. A solution of compound 7 (1.8 g, 7.4 mmol, 1.0 eq.) in THF (20 ml) was added dropwise at −78° C. and the reaction mixture was allowed to warm to RT in 2 h. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with water (60 ml) while cooling and extracted with ethyl acetate (2×50 ml). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to give the crude product which was purified by column chromatography (neutral alumina; 0.5% MeOH/MC) to yield compound 8 as a light yellow semisolid. Yield: 46% (1.1 g, 3.42 mmol).

Step-8: 8-(Pyridin-4-yl)-2-azaspiro[4.5]decan-8-ol (AMN-39)

A solution of compound 8 (500 mg, 1.55 mmol, 1.0 eq.) in MeOH (15 ml) was degassed with argon for 15 min followed by addition of Pd(OH)₂ (250 mg). The reaction mixture was stirred under H₂ balloon pressure for 4 h. After completion of the reaction (monitored by TLC), the reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure to yield AMN-39 as a white solid which was used in the next step without further purification. Yield: 88% (320 mg, 1.38 mmol).

Synthesis of the Amine Unit AMN-41 8-(5-(Trifluoromethyl)pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane (AMN-41) Step-1: tert-Butyl 8-(5-(trifluoromethyl)pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate

Sodium t-butoxide (625 mg, 6.51 mmol, 3.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (600 mg, 2.17 mmol, 1.0 eq.) and 2-chloro-5-(trifluoromethyl)pyrimidine (391 mg, 2.17 mmol, 1.0 eq.) in toluene (15 ml) and the reaction mixture was degassed with nitrogen. BINAP (80 mg, 0.13 mmol, 0.06 eq.) and Pd(OAc)₂ (10 mg, 0.04 mmol, 0.02 eq.) were added and the resulting mixture was heated at 120° C. for 16 h. The reaction mixture was filtered through celite and the filtrate was evaporated under reduced pressure to afford the crude product which was purified by column chromatography (silica gel; 0-1% MeOH/MC) to yield the pure desired product as a white solid. Yield: 41% (350 mg, 1.2 mmol).

Step-2: 8-(5-(Trifluoromethyl)pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane (AMN-41)

TFA (1.5 ml) was added to a solution of tert-butyl 8-(5-(trifluoromethyl)pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (300 mg, 0.78 mmol, 1.0 eq.) in methylene chloride (6 ml) at 0° C. and the reaction mixture was stirred at 25° C. for 1 h. After completion of the reaction, the solvent was evaporated under reduced pressure to give the desired product as a yellow sticky solid which was directly used in the next step.

Synthesis of the Amine Unit AMN-42 9-(1H-Imidazol-1-yl)-3-azaspiro[5.5]undecane (AMN-42) Step-1: tert-Butyl 9-(methylsulfonyloxy)-3-azaspiro[5.5]undecane-3-carboxylate

Methanesulfonyl chloride (0.98 ml, 12.27 mmol, 1.5 eq.) was added to a solution of tert-butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate (2.20 g, 8.18 mmol, 1.0 eq.) (see step-6 product of AMN-38) and Et₃N (2.84 ml, 20.45 mmol, 2.5 eq.) in MC (20 ml) at 0° C. and the resulting reaction mixture was stirred at RT for 14 h. The reaction mixture was diluted with MC (50 ml) and washed with sat. NH₄Cl solution (2×25 ml) and brine (2×25 ml) and then dried over sodium sulfate. The solvent was removed under reduced pressure and the crude product was purified by column chromatography (silica gel; 10% ethyl acetate/hexanes) to give the desired compound as a light orange solid. Yield: 88% (2.84 g, 8.18 mmol).

Step-2: tert-Butyl 9-(1H-imidazol-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate

Imidazole (1.17 g, 17.3 mmol, 3.0 eq.) was added to a stirred suspension of NaH (20.16 mmol, 3.5 eq.) in DMF (10 ml) at 0° C. and the reaction mixture was allowed to stir at the same temperature for 20 min. A solution of tert-butyl 9-(methylsulfonyloxy)-3-azaspiro[5.5]undecane-3-carboxylate (2.0 g, 5.76 mmol, 1.0 eq.) in DMF (5 ml) was added to the reaction mixture at 0° C. and it was stirred at RT for 16 h. The reaction mixture was diluted with water (50 ml) and extracted with ethyl acetate (3×50 ml). The combined organic layers were washed with brine (60 ml) and dried over sodium sulfate. The solvent was evaporated under reduced pressure to obtain the crude product which was purified by column chromatography (silica gel; 3% MeOH/MC) to yield the desired product as a colorless oil. Yield: 59% (1.10 g, 3.45 mmol).

Step-3: 9-(1H-Imidazol-1-yl)-3-azaspiro[5.5]undecane (AMN-42)

TFA (2 ml) was added to a solution of tert-butyl 9-(1H-imidazol-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate (1.10 g, 3.45 mmol, 1.0 eq.) in MC (10 ml) at 0° C. and the resulting reaction mixture was stirred at 25° C. for 2 h. The solvent was evaporated under reduced pressure and the residue was azeotroped twice with MC to get the desired product.

Synthesis of the Amine Unit AMN-43 8-(Pyridin-4-yl)-2-azaspiro[4.5]decane (AMN-43) Step-1: 2-Benzyl-8-(pyridin-4-yl)-2-azaspiro[4.5]dec-7-ene

To a solution of 2-benzyl-8-(pyridin-4-yl)-2-azaspiro[4.5]decan-8-ol (500 mg, 1.55 mmol, 1.0 eq.) (see step-7 product AMN-39) in pyridine (5 ml) was added dropwise SOCl₂ (1 ml) at −10° C. and the reaction mixture was stirred at the same temperature for 10 min. After completion of the reaction (monitored by TLC), the reaction mixture was poured onto (50 g) and sat. NaHCO₃ solution (10 ml) was added. The mixture was extracted with methylene chloride (50 ml). The organic layer was washed with brine (30 ml) and dried over sodium sulfate. The solvent was evaporated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 2% MeOH/DCM) to yield the desired compound as a yellow semisold. Yield: 63% (300 mg, 0.987 mmol).

Step-2: 8-(Pyridin-4-yl)-2-azaspiro[4.5]decane (AMN-43)

A solution of benzyl-8-(pyridin-4-yl)-2-azaspiro[4.5]dec-7-ene (300 mg, 0.987 mmol, 1.0 eq.) in MeOH (10 ml) was degassed with argon for 15 min followed by addition of Pd(OH)₂ (150 mg). The reaction mixture was stirred under H₂ balloon pressure for 4 h. After completion of the reaction (monitored by LCMS), the reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure to yield the desired compound as an off-white solid which was used in the next step without further purification. Yield: 80% (170 mg, 0.787 mmol).

Synthesis of the Amine Unit AMN-44 8-(Pyridin-3-yl)-2-azaspiro[4.5]decane (AMN-44) Step-1: 2-Benzyl-8-(pyridin-3-yl)-2-azaspiro[4.5]decan-8-ol

A solution of 3-bromopyridine (290 μl, 2.96 mmol, 1.20 eq.) in dry THF (9 ml) was added dropwise to a solution of n-BuLi (2.47 ml, 4.94 mmol, 2.0 eq., 2M solution in hexane) in THF (9 ml) at −78° C. and the reaction mixture was stirred at same temperature for 1 h. A solution of 2-benzyl-2-azaspiro[4.5]decan-8-one (600 mg, 2.47 mmol, 1.0 eq.) (see step-6 product AMN-39) in THF (10 ml) was added dropwise at −78° C. and the reaction mixture was stirred at the same temperature for 1 h. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with water (15 ml) while cooling and extracted with ethyl acetate (2× ml). The combined organic layers were washed with water (20 ml) and brine (20 ml), and dried over sodium sulfate. The solvent was evaporated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 10% MeOH/MC) to yield the desired compound as a light brown semi-solid. Yield: 44% (350 mg, 1.08 mmol).

Step-2: 2-Benzyl-8-(pyridin-3-yl)-2-azaspiro[4.5]dec-7-ene

SOCl₂ (1 ml) was added dropwise to a solution of 2-benzyl-8-(pyridin-3-yl)-2-azaspiro[4.5]decan-8-ol (450 mg, 1.39 mmol, 1.0 eq.) in pyridine (5 ml) at −10° C. and the reaction mixture was stirred at the same temperature for 15 min. After completion of the reaction (monitored by TLC), the reaction mixture was poured onto crushed ice and the mixture was then neutralized with sat. NaHCO₃ solution (15 ml). It was extracted with methylene chloride (2×30 ml) and the combined organic layers were washed with water (20 ml) and brine (20 ml), and dried over sodium sulfate. The solvent was evaporated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 10% MeOH/DCM) to yield the desired compound as a reddish sticky solid. Yield: 71% (300 mg, 0.99 mmol).

Step-3: 8-(Pyridin-3-yl)-2-azaspiro[4.5]decane

A solution of 2-benzyl-8-(pyridin-3-yl)-2-azaspiro[4.5]dec-7-ene (250 mg, 0.822 mmol, 1.0 eq.) in MeOH (15 ml) was degassed with argon for 15 min, followed by addition of Pd(OH)₂ (125 mg, 50% by wt.). The reaction mixture was stirred under H₂ balloon pressure for 4.5 h at RT. After completion of the reaction (monitored by LCMS), the reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure to yield the desired compound as an off-white solid which was used in the next step without further purification. Yield: 93% (165 mg, 0.76 mmol).

Synthesis of the Amine Unit AMN-45 3-(Pyridin-4-yl)-3,9-diazaspiro[5.6]dodecane (AMN-45) Step-1:1-Benzylazepan-4-one

To a suspension of azepan-4-one (8.0 g, 53.47 mmol, 1.0 eq.) in methylene chloride (100 ml) was added TEA followed by benzaldehyde and reaction mixture was stirred at RT for 30 min. Na(OAc)₃BH was added portionwise to the reaction mixture and it was then stirred at RT for another 4 h. The reaction mixture was quenched with NaOH (2 M, 80 ml) and extracted with methylene chloride (3×100 ml). The organic layer was dried over Na₂SO₄ and solvent was evaporated under reduced pressure to afford the crude product which was purified by column chromatography (silica gel, 20% EtOAc/hexanes) to yield the desired product as an oil. Yield: 78% (8.5 g, 41.87 mmol).

Step-2: 9-Benzyl-2,4-dioxo-3,9-diazaspiro[5.6]dodecane-1,5-dicarbonitrile

To a mixture of 1-benzylazepan-4-one (10.0 g, 49.2 mmol, 1.0 eq.) and ethyl cyanoacetate (12.2 g, 108.3 mmol, 2.2 eq.) was added EtOH—NH₃ (50 ml) at −10° C. and it was stirred for 30 min. Then the reaction flask was sealed and kept inside a deep refrigerator (−5 to −10° C.) for 7 d. The solvent was removed under reduced pressure and the crude solid material was washed with ether (3×100 ml) to afford the desired solid product which was used in the next step without further purification.

Step-3: 2,2′-(1-Benzylazepane-4,4-diyl)diacetic acid

65% H₂SO₄ (17.5 ml) was added to a solid powder of 9-benzyl-2,4-dioxo-3,9-diazaspiro[5.6]dodecane-1,5-dicarbonitrile (3.5 g, 10.4 mmol) and the reaction mixture was heated at reflux for 2 h. Then the reaction mixture was cooled to RT, water (6.1 ml) was added and it was again heated at reflux for 20 h. After cooling to 0° C., the reaction mixture was first basified to pH ˜10-12 using 40% NaOH solution and then acidified to pH ˜2-3 using 2 N HCl solution. The solvent was removed under reduced pressure and the residue was dried by azeotropic distillation with benzene. Residual benzene was removed under reduced pressure to afford the dry solid product which was used in the next step without further purification.

Step-4: Diethyl 2,2′-(1-benzylazepane-4,4-diyl)diacetate

A mixture of 2,2′-(1-benzylazepane-4,4-diyl)diacetic acid (3.5 g, 10.4 mmol), EtOH (100 ml) and H₂SO₄ (5 ml) was heated at reflux for 16 h. The solvent was removed under reduced pressure and the solid material was dissolved in water (100 ml) and basified with sat Na₂CO₃ solution to pH ˜10. The desired compound was then extracted from the mixture with ethyl acetate (3×100 ml), dried over Na₂SO₄ and evaporated under reduced pressure. The crude material was purified through column chromatography (silica gel, 1.5% MeOH/MC) to yield the desired product as a brown oil. Yield: 26% (1.0 g, 2.78 mmol).

Step-5: 2,2′-(1-Benzylazepane-4,4-diyl)diethanol

Diethyl 2,2′-(1-benzylazepane-4,4-diyl)diacetate (1.0 g, 2.77 mmol, 1.0 eq.) in THF (10 ml) was added to a suspension of LAH (315 mg, 8.3 mmol, 3.0 eq.) in THF (40 ml) at 0° C. and the mixture was stirred at RT for 20 h. The reaction mixture was then quenched with a mixture of H₂O-THF (1:10, 4 ml), stirred for 15 min and filtered through celite. The filtrate was concentrated under reduced pressure and the crude product thus obtained was used in the next step without further purification.

Step-6: tert-Butyl 4,4-bis(2-hydroxyethyl)azepane-1-carboxylate

A mixture of 2,2′-(1-benzylazepane-4,4-diyl)diethanol (1.5 g, 5.4 mmol, 1.0 eq.) in methanol (30 ml) and Boc-anhydride (1.2 ml, 6.47 mmol, 1.2 eq.) was degassed with nitrogen for 30 mins. Then Pd—C (1 g) was added to the mixture and it was stirred at RT under H₂ balloon pressure for 16 h. After completion of the reaction (monitored by TLC) the mixture was filtered through celite and the residue washed with methanol (100 ml). The filtrate and washings were then concentrated to afford the desired compound as a brown sticky compound. Yield: 52% (800 mg, 2.78 mmol).

Step-7: tert-Butyl 4,4-bis(2-(methylsulfonyloxy)ethyl)azepane-1-carboxylate

TEA (1.1 ml, 8.36 mmol, 3.0 eq.) was added to a cooled solution of tert-butyl 4,4-bis(2-hydroxyethyl)azepane-1-carboxylate (800 mg, 2.78 mmol, 1.0 eq.) in methylene chloride (10 ml) at 0° C. and then mesylchloride (0.47 ml, 6.13 mmol, 2.2 eq.) was added to the reaction mixture and it was stirred at RT for 2 h. After completion (monitored by TLC), the reaction mixture was diluted with water (20 ml) and methylene chloride (100 ml). The organic part was separated and the water layer was extracted with methylene chloride (2×20 ml). The combined organic layers were washed with brine (20 ml), dried over Na₂SO₄ and concentrated under reduced pressure to give the crude product which was used in the next step without further purification.

Step-8: tert-Butyl 3,9-diazaspiro[5.6]dodecane-9-carboxylate

A mixture of tert-butyl 4,4-bis(2-(methylsulfonyloxy)ethyl)azepane-1-carboxylate (500 mg, 1.12 mmol), MeOH (2 ml) and NH₃ solution (1.5 ml) was heated at 50° C. in a sealed tube for 16 h. The reaction mixture was concentrated under reduced pressure and the crude material was washed with hexanes and dried to afford the desired compound as a yellowish semi-solid which was used in the next step without further purification.

Step-9: tert-Btyl 3-(pyridin-4-yl)-3,9-diazaspiro[5.6]dodecane-9-carboxylate

A mixture of tert-butyl 3,9-diazaspiro[5.6]dodecane-9-carboxylate (300 mg, 1.1 mmol, 1.0 eq.), 4-bromo pyridine (260 mg, 1.34 mmol, 1.2 eq.) and DIPEA (0.2 ml, 1.49 mmol, 2.0 eq.) in n-butanol (4 ml) was heated at reflux for 48 h. After completion (monitored by LCMS) the reaction mixture was concentrated and the crude product was purified by column chromatography (alumina, 5% MeOH/MC) to yield the pure product as an off-white solid. Yield: 52% (200 mg, 0.579 mmol).

Step-10: 3-(Pyridin-4-yl)-3,9-diazaspiro[5.6]dodecane (AMN-45)

TFA (1.0 ml) was added to a solution of tert-butyl 3-(pyridin-4-yl)-3,9-diazaspiro[5.6]dodecane-9-carboxylate (250 mg, 0.724 mmol) in methylene chloride (3 ml) at 0° C. and the resulting reaction mixture was stirred at RT for 2 h. The solvent was evaporated under reduced pressure and the residue was azeotroped with toluene to give the desired product which was used in the next step without further purification.

Synthesis of the Amine Unit AMN-46 4-(2,8-Diazaspiro[4.5]decan-8-yl)benzonitrile (AMN-46) Step-I: tert-Butyl 8-(4-cyanophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate

Cesium carbonate (1.35 g, 4.16 mmol, 2.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (500 mg, 2.08 mmol, 1.0 eq.) and 4-chlorobenzonitrile (390 mg, 2.08 mmol, 1.0 eq.) in toluene (30 ml) and the reaction mixture was degassed with nitrogen for 15 min. BINAP (52 mg, 0.083 mmol, 0.04 eq.) and Pd(OAc)₂ (10 mg, 0.0416 mmol, 0.02 eq.) were added and the resulting reaction mixture was heated at reflux for 16 h. The reaction mixture was filtered through celite and the filtrate was evaporated under reduced pressure to afford the crude product which was purified by column chromatography (silica gel; 15-20% EtOAc/hexanes) to yield the pure product as an oil. Yield: 49% (350 mg, 1.026 mmol).

Step-II: -(2,8-Diazaspiro[4.5]decan-8-yl)benzonitrile (AMN-46)

TFA (2.5 ml) was added to a solution of tert-butyl 8-(4-cyanophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate (350 mg, 1.026 mmol, 1.0 equiv.) in methylene chloride (6 ml) at 0° C. and the reaction mixture was stirred at RT for 1 h. After completion of the reaction, the solvent was evaporated under reduced pressure to give the desired product as a yellow sticky solid which was used in the next step without further purification.

Synthesis of the Amine Unit AMN-47 8-(4-Methoxyphenyl)-2,8-diazaspiro[4.5]decane (AMN-47) Step-I: tert-Butyl 8-(4-methoxyphenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate

Sodium t-butoxide (599 mg, 6.24 mmol, 3.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (500 mg, 2.08 mmol, 1.0 eq.) and 1-chloro-4-methoxybenzene (389 mg, 2.08 mmol, 1.0 eq.) in toluene (25 ml) and the reaction mixture was degassed with Nitrogen. BINAP (51.8 mg, 0.083 mmol, 0.04 eq.) and Pd(OAc)₂ (10 mg, 0.0416 mmol, 0.02 equiv) were added and the resulting mixture was heated at reflux for 16 h. The reaction mixture was filtered through celite and the filtrate was evaporated under reduced pressure to afford the crude product which was purified by column chromatography (silica gel; 0-10% EtOAc/hexanes) to give the pure product as an oil. Yield: 35% (250 mg, 0.722 mmol).

Step-II: 8-(4-Methoxyphenyl)-2,8-diazaspiro[4.5]decane (AMN-47)

TFA (1.2 ml) was added to a solution of tert-butyl 8-(4-methoxyphenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate (200 mg, 0.57 mmol, 1.0 eq.) in methylene chloride (5 ml) at 0° C. and the reaction mixture was stirred at RT for 1 h. After completion of the reaction, the solvent was evaporated under reduced pressure to give the desired product as a yellow sticky solid which was used in the next step without further purification.

C. Syntheses of Individual Substances General Method for Synthesis of the Dihydroindene Derivatives (H)

1) Synthesis of the Dihydroindene Derivatives I General Working Instructions 1 (GWI-1):

1-Hydroxybenzotriazole hydrate (0.3 eq.) and N-ethyl-diisopropylamine (4 eq.) were added to a solution of (G) (1.5 eq.) in methylene chloride. The reaction mixture was cooled to 0° C. and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.5 eq.) was then added. The mixture was stirred at this temperature for 15 min, before the amine (1 eq.) was finally added. The reaction mixture was then stirred at room temperature overnight. For working up, the reaction mixture was washed 3× with 0.5 M KOH solution and the organic phase was dried over MgSO₄, filtered and concentrated. The crude product was either purified by column chromatography (silica; methylene chloride/methanol or aluminium oxide; methylene chloride/methanol) or recrystallized from methylene chloride to obtain the product (H) in a pure form.

General Working Instructions 2 (GWI-2):

O-(1H-Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (1 eq.) and 1-hydroxybenzotriazole hydrate (1 eq.) were added to a solution of (G) (1 eq.) in tetrahydrofuran and the reaction mixture was stirred at room temperature for 0.5 h. The amine (0.9 eq.) and N-ethyl-diisopropylamine (2.5 eq.) were then added and the mixture was stirred at room temperature overnight. For working up, the reaction mixture was concentrated, methylene chloride and sat. NaHCO₃ solution were added to the residue and the aqueous phase was extracted with methylene chloride a further 2×. The combined organic phases were washed with sat. NaCl solution a further 1×, dried over Na₂SO₄, filtered and concentrated. The crude product was purified by column chromatography (silica; ethyl acetate/methanol/NH₃ 10:1:0.05) to obtain the product (H) in a pure form.

General Working Instructions 3 (GWI-3):

1,1′-Carbonyldiimidazole (2 eq.) was added to a solution of (G) (1 eq.) in methylene chloride and N,N-dimethylformamide and the reaction mixture was stirred at room temperature for 1 h. The amine (1 eq.), dissolved in methylene chloride (230 eq.), N,N-dimethylformamide (26 eq.) and N-ethyl-diisopropylamine (5 eq.), was then added and the mixture was stirred at room temperature overnight. For working up, sat. NaHCO₃ solution was added to the reaction mixture and the mixture was stirred for 15 min. The aqueous phase was extracted with methylene chloride a further 1×. The combined organic phases were concentrated. The crude product was purified via HPLC to obtain the product (H) in a pure form.

General Working Instructions 4 (GWI-4):

O-(7-Azabenzotriazol-1-yl)N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.1 eq.) and N-ethyl-diisopropylamine (2.5 eq.) were added to a solution of the corresponding carboxylic acid (1 eq.) in tetrahydrofuran at 0° C. and the reaction mixture was stirred at room temperature for 0.5 h. The corresponding amine (1 eq.) was then added and the mixture was stirred at room temperature overnight. For working up, the reaction mixture was diluted with ethyl acetate and washed with sat. NaHCO₃ solution, NH₄Cl solution, dist. water and sat. NaCl solution. The combined organic phases were dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (silica; ethyl acetate/ethanol/ammonia (25% aq.) in order to obtain the product (H) in a pure form.

General Working Instructions 5 (GWI-5):

N-Ethyl-diisopropylamine (4 eq.) was added to a solution of the corresponding carboxylic acid (1 eq.) in methylene chloride. The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before the corresponding amine (1.1 eq.) was finally added. The reaction mixture was then stirred at room temperature overnight. For working up, the reaction mixture was washed in each case 1× with 10% strength NH₄Cl solution, sat. NaHCO₃ solution and sat. NaCl solution. The organic phase was dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (silica; ethyl acetate/ethanol/ammonia (25% aq.) in order to obtain the product (H) in a pure form.

Notes:

-   (a) In most cases the no. of equivalents of amine was reduced     slightly to 1 eq. -   (b) In some cases the no. of equivalents of N-ethyl-diisopropylamine     was adapted as required to between 3.0 and 5.0 eq., in most cases     4.5 eq. were employed. -   (c) Typical reaction times were overnight to 2.5 d. -   (d) Alternatively to drying the organic fraction after work-up over     sodium sulfate magnesium sulfate was used in some cases.

General Working Instructions 6 (GWI-6):

HATU (1.1 eq.) and DIPEA (2.5 eq.) were added to a suspension of the corresponding carboxylic acid (1.0 eq.) in THF (5 ml) at 0° C. and the reaction mixture was stirred for 15 min. A solution of the corresponding amine (1.0 eq.) in THF (1 ml) was added to the reaction mixture and the mixture was stirred at 25° C. for approx. 12 h or until the reaction was complete. The reaction mixture was diluted with methylene chloride or ethyl acetate, washed successively with NaHCO₃ solution, NH₄Cl solution, water and sat. NaCl solution and dried over sodium sulfate. The solvent was removed in vacuo in order to obtain the crude material, which was purified by column chromatography (silica gel, methanol/methylene chloride) in order to obtain the final product (H).

General Working Instructions 7 (GWI-7):

DIPEA (4.0 eq.) was added to a solution of the corresponding carboxylic acid (1.0 eq.) in CH₂Cl₂ at 0° C., followed by EDCI (1.5 eq.) and HOBT (1.0 eq.). The reaction mixture obtained was stirred at 25° C. for 15 min and then cooled again to 0° C. A solution of the corresponding amine (1.2 eq.) in CH₂Cl₂ was added to the reaction mixture and the mixture was stirred at 25° C. for approx. 16 h or until the reaction was complete. The mixture was diluted with methylene chloride and washed with sat. NH₄Cl solution, sat. NaHCO₃ solution and sat. NaCl solution. The organic phase was dried over sodium sulfate and concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, methanol/methylene chloride) in order to obtain the final product (H).

General Working Instructions 8 (GWI-8):

N-Ethyl-diisopropylamine (4 eq.) was added to a solution of the corresponding carboxylic acid (1 eq.) in methylene chloride. The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before the corresponding amine (1 eq.) was added. The reaction mixture was stirred at room temperature overnight. Then, the reaction mixture was concentrated. The white residue was taken up in ethyl acetate and methylene chloride (1:1) and the mixture stirred at 50° C. for ½ h. The white solid was filtered out and dried in vacuo in order to obtain the final product (H).

Note: H-23 & H-24 & H-64 The hydrochloride was precipitated with 2 mol/l of HCl in diethyl ether.

TABLE Synthesis of the dihydroindene derivatives (H) Amino Synthesis Exam- acid Amine accord- ple no. Structure Name (ACI) (AMN) ing to Yield Comments H-01

7-chloro-2-[6-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-2,3- dihydro-isoindol-1-one (H-01) (G-01) (AMN-01) GWI-1 69% (0.27 mmol) purification by column chromatography: MC/MeOH 99:1 → 96:4 H-02

2-chloro-N-[6-(3-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-9- carbonyl)-2,3-dihydro-1H-inden- 1-yl]-benzamide (H-02) (E-01) (AMN-01) GWI-1 27% (0.54 mmol) purification by column chromatography: silica; MC/MeOH H-03

4-methoxy-2,6-dimethyl-N-[6-(9- pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzene- sulfonic acid amide (H-03) (F-01) (AMN-01) GWI-1 68% (0.24 mmol) Recrystallization from MC H-04

2-chloro-N-[6-(8-pyridin-4-yl-3(8- diazaspiro[4.4]nonane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzamide (H-04) (E-01) (AMN-02) GWI-2 80% (0.38 mmol) purification by column chromatography: silica; EA:MeOH: ammonia 10:1:0.05 H-05

2-chloro-N-[6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]- benzamide (H-05) (E-01) (AMN-03) GWI-2 66% (0.52 mmol) purification by column chromatography: silica; EA:MeOH: ammonia 10:1:0.05 H-06

N-[6-[9-(azetidin-1-yl)-3- azaspiro[5.5]undecane-3- carbonyl]-2,3-dihydro-1H- inden-1-yl]-2-chloro- benzamide (H-06) (E-01) (AMN-04) GWI-2 81% (0.51 mmol) purification by column chromatography: silica; ethyl acetate/methanol 4:1 + NH₃ H-07

2-chloro-N-[6-[9-(3,3-difluoro-azetidin- 1-yl)-3-azaspiro[5.5]undecane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-07) (E-01) (AMN-05) GWI-2 73% (0.46 mmol) purification by column chromatography: silica; ethyl acetate/hexane 5:1 H-08

2-chloro-N-[6-(9-pyridin-4-yloxy-3- azaspiro[5.5]undecane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-08) (E-01) (AMN-06) GWI-2 77% (0.61 mmol) purification by column chromatography: silica; EA:MeOH: ammonia 10:1:0.05 H-09

2-chloro-N-[(1R)-7-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-09) (E-06) (AMN-01) GWI-2 73% (0.44 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-10

2-chloro-N-[(1S)-7-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-10) (E-07) (AMN-01) GWI-2 73% (0.44 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-11

2-chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-11) (E-06) (AMN-03) GWI-2 99% (0.45 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-12

2-chloro-N-[(1S)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-12) (E-07) (AMN-03) GWI-2 99% (0.36 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-13

7-chloro-2-[(1R)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- 2,3-dihydro-isoindol-1-one (H-13) (G-03) (AMN-03) GWI-2 97% (0.43 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-14

7-chloro-2-[(1R)-7-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- 2,3-dihydro-isoindol-1-one (H-14) (G-03) (AMN-01) GWI-2 89% (0.46 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-15

7-chloro-2-[(1S)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- 2,3-dihydro-isoindol-1-one (H-15) (G-02) (AMN-03) GWI-2 93% (0.46 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-16

4-methoxy-2,6-dimethyl-N-[(1R)-7-(8- pyridin-4-yl-3,8-diazaspiro[4.5]decane- 3-carbonyl)-1,2,3,4-tetrahydro- naphthalen-1-yl]-benzenesulfonic acid amide(H-16) (F-03) (AMN-03) GWI-2 97% (0.32 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-17

4-methoxy-2,6-dimethyl-N-[(1R)-7-(9- pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzenesulfonic acid amide (H-17) (F-03) (AMN-01) GWI-2 65% (0.33 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-18

4-methoxy-2,6-dimethyl-N-[(1S)-7-(8- pyridin-4-yl-3,8-diazaspiro[4.5]decane- 3-carbonyl)-1,2,3,4-tetrahydro- naphthalen-1-yl]-benzenesulfonic acid amide(H-18) (F-02) (AMN-03) GWI-2 84% (0.32 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-19

4-methoxy-2,6-dimethyl-N-[(1S)-7-(9- pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzenesulfonic acid amide (H-19) (F-02) (AMN-01) GWI-2 86% (0.19 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-20

2-chloro-N-[(1S)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H- 20) (E-02) (AMN-03) GWI-2 43% (0.27 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-21

2-chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H- 21) (E-03) (AMN-03) GWI-2 92% (0.87 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-22

2-chloro-N-[(1R)-7-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-22) (E-05) (AMN-01) GWI-2 89% (0.28 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine H-23

2-chloro-N-[(1S)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide hydrochloride (H-23) (E-05) (AMN-03) GWI-2 69% (0.22 mmol) 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine plus HCl precipitation H-24

2-chloro-N-[(1S)-7-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-24) (E-04) (AMN-03) GWI-4 65% (0.31 mmol) HCl precipitation H-25

2-chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide hydrochloride (H-25) (E-04) (AMN-01) GWI-4 71% (0.25 mmol) H-26

2-chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-26) (E-03) (AMN-07) GWI-5 89% (0.28 mmol) H-27

2-chloro-N-[(1R)-6-(7-pyridin-4-yl-2,7- diazaspiro[3.5]nonane-2-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-27) (E-03) (AMN-08) GWI-5 92% (0.44 mmol) H-28

2-chloro-N-[(1R)-6-[9-(1-methyl-piperidin- 4-yl)-3,9-diazaspiro[5.5]undecane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-28) (E-03) (AMN-09) GWI-5 29% (0.09 mmol) H-29

2-chloro-N-[(1R)-6-[9-(4-methyl- piperazine-1-carbonyl)-3- azaspiro[5.5]undecane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-29) (E-03) (AMN-10) GWI-5 88% (0.36 mmol) H-31

2-chloro-N-[(1R)-6-[9-[(1-methyl-piperidin- 4-yl)-methyl]-3,9-diazaspiro[5.5]undecane- 3-carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-31) (E-03) (AMN-12) GWI-5 33% (0.11 mmol) H-32

2-chloro-N-[(1R)-6-(spiro[1H-furo[3,4- c]pyridine-3,4′-piperidine]-1′-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-32) (E-03) (AMN-13) GWI-4 99% (0.41 mmol) H-33

2-chloro-N-[(1R)-6-(8-pyridin-4-yl-4,8- diazaspiro[5.5]undecane-4-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-33) (E-03) (AMN-14) GWI-5 60% (0.28 mmol) H-34

2-chloro-N-[(1R)-6-(7-pyridin-4-yl-3,7- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-34) (E-03) (AMN-15) GWI-5 71% (0.27 mmol) H-35

2-chloro-N-[(1R)-6-(2-pyridin-4-yl-2,9- diazaspiro[4.5]decane-9-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-35) (E-03) (AMN-16) GWI-5 92% (0.35 mmol) H-36

N-[(1R)-6-[9-(4-tert-Butyl-piperazin-1-yl)- 3-azaspiro[5.5]undecane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-2-chloro- benzamide (H-36) (E-03) (AMN-17) GWI-5 61% (0.39 mmol) H-37

2-chloro-N-[(1R)-6-[9-(pyrrolidine-1- carbonyl)-3-azaspiro[5.5]undecane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-37) (E-03) (AMN-18) GWI-4 95% (0.51 mmol) H-38

2-chloro-N-[(1R)-6-[8-(2-pyrrolidin-1-yl- acetyl)-3,8-diazaspiro[4.5]decane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-38) (E-03) (AMN-19) GWI-4 58% (0.109 mmol) H-39

2-chloro-N-[6-(8-pyridin-2-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-39) (E-01) (AMN-20) GWI-6 42% H-40

2-chloro-N-[6-[8-(4-chlorophenyl)-3,8- diazaspiro[4.5]decane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-40) (E-01) (AMN-21) GWI-7 52% H-41

2-chloro-N-[6-[8-(4-fluorophenyl)-3,8- diazaspiro[4.5]decane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-41) (E-01) (AMN-22) GWI-7 65% H-42

2-chloro-N-[6-[8-[4-(trifluoromethyl)- phenyl]-3,8-diazaspiro[4.5]decane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-42) (E-01) (AMN-23) GWI-7 50% H-43

2-chloro-N-[6-(8-pyridin-3-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-43) (E-01) (AMN-24) GWI-7 30% H-44

2-chloro-N-[6-(8-pyrimidin-2-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-44) (E-01) (AMN-25) GWI-6 42% H-45

2-chloro-N-[6-[8-[2-(trifluoromethyl)- pyridin-4-yl]-3,8-diazaspiro[4.5]decane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-45) (E-01) (AMN-26) GWI-6 55% H-46

2-chloro-N-[6-[8-[8-(trifluoromethyl)- quinolin-4-yl]-3,8-diazaspiro[4.5]decane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-46) (E-01) (AMN-27) GWI-6 30% HATU (1 equiv.), DIPEA (3 equiv.) H-47

2-chloro-N-[2,2-dimethyl-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-1,3- dihydro-inden-1-yl]-benzamide (H-47) (E-08) (AMN-03) GWI-7 30% H-48

2-chloro-N-[6-[8-[5-(trifluoromethyl)- pyridin-2-yl]-3,8-diazaspiro[4.5]decane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-48) (E-01) (AMN-28) GWI-6 29% HATU (1.2 equiv.), DIPEA (3 equiv.) H-49

2-chloro-N-methyl-N-[6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-49) see below H-50

2-chloro-N-[6-(8-isoquinolin-6-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-50) (E-01) (A-29) GWI-6 58% HATU (1.1 equiv.), DIPEA (2.5 equiv.) H-51

2-chloro-N-[6-[8-[2-(trifluoromethyl)- pyrimidin-4-yl]-3,8-diazaspiro[4.5]decane- 3-carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-51) (E-01) (A-30) GWI-6 30% HATU (1.1 equiv.), DIPEA (3.5 equiv.) H-52

N-[(5R)-1-Azabicyclo[2.2.2]octan-5-yl]-3- [(3R)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carbonyl]-3- azaspiro[5.5]undecane-9-carboxylic acid amide (H-52) (E03) (AMN-31) GWI-5 37% H-53

2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-53) (E-09) (AMN-03) GWI-5 56% (reaction times were adapted) H-54

2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-2,9- diazaspiro[5.5]undecane-2-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-54) see below H-55

2-Chloro-N-[(1R)-6-[9-(5,6,7,8-tetrahydro- [1,2,4]triazolo[1,5-a]pyrazin-7-yl)-3- azaspiro[5.5]undecane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-55) (E03) (AMN-32) GWI-5 77% H-56

6-Methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-naphthalene-2- carboxylic acid amide (H-56) (E-10) (AMN-03) GWI-5 86% H-57

2-Chloro-N-[(4R)-6-(3-pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-3,4- dihydro-2H-chromen-4-yl]-benzamide (H- 57) (E-11) (AMN-33) GWI-5 67% H-58

2-Chloro-N-[(4R)-6-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-3,4- dihydro-2H-chromen-4-yl]-benzamide (H- 58) (E-11) (AMN-01) GWI-5 93% H-59

2-Chloro-N-[(1R)-5-methyl-6-(3-pyridin-4- yl-3,8-diazaspiro[4.5]decane-8-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H- 59) (E-12) (AMN-33) GWI-5 62% H-60

2-Chloro-4-methoxy-N-[(1R)-6-(3- pyridin-4-yl-3,8-diazaspiro[4.5]decane- 8-carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-60) (E-13) (AMN-33) GWI-5 82% H-61

4-Methoxy-2-methyl-N-[(1R)-6-(8-pyridin- 4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-61) (E-14) (AMN-03) GWI-5 88% H-62

N-[(5S)-1-Azabicyclo[2.2.2]octan-5-yl]-3- [(3R)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carbonyl]-3- azaspiro[5.5]undecane-9-carboxylic acid amide (H-62) (E03) (AMN-34) GWI-5 19% H-63

2-Chloro-4-methoxy-N-[(1R)-6-(8-pyridin- 4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-63) (E-13) (AMN-03) GWI-5 99% H-64

2-Chloro-N-[(1R)-5-fluoro-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide hydrochloride (H-64) (E-15) (AMN-03) GWI-5 28% HCl-salt precipitation with 3 equiv. HCl in diethyl ether/acetone H-65

2-Chloro-N-[(4R)-7-fluoro-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-3,4- dihydro-2H-chromen-4-yl]-benzamide (H- 65) (E-16) (AMN-03) GWI-5 35% H-66

2-Chloro-N-[(1R)-5-methyl-6-(9-pyridin-4- yl-3,9-diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-66) (E-12) (AMN-01) GWI-5 90% H-67

2-Chloro-N-[(4R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-3,4- dihydro-2H-chromen-4-yl]-benzamide (H- 67) (E-11) (AMN-03) GWI-5 83% H-68

6-Methoxy-N-[(1R)-6-(3-pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-naphthalene-2- carboxylic acid amide (H-68) (E-10) (AMN-33) GWI-5 >99%  H-69

2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-4,8- diazaspiro[5.5]undecane-4-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-69) (E-06) (AMN-14) GWI-5 64% H-70

2-Chloro-N-[(1R)-7-(2-pyridin-4-yl-2,9- diazaspiro[4.5]decane-9-carbonyl)-1,2,3,4- tetrahydro-naphthalen-1-yl]-benzamide (H- 70) (E-06) (AMN-15) GWI-5 70% H-71

2-Chloro-N-[(1R)-7-(7-pyridin-4-yl-2,7- diazaspiro[3.5]nonane-2-carbonyl)-1,2,3,4- tetrahydro-naphthalen-1-yl]-benzamide (H- 71) (E-06) (AMN-08) GWI-5 80% H-72

2-Chloro-N-[(1R)-7-(3-pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-1,2,3,4- tetrahydro-naphthalen-1-yl]-benzamide (H- 72) (E-06) (AMN-33) GWI-8 75% H-73

2-Chloro-N-[(4R)-8-fluoro-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-3,4- dihydro-2H-chromen-4-yl]-benzamide (H- 73) (E-17) (AMN-03) GWI-5 85% H-74

2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-4- (trifluoromethyloxy)-benzamide (H-74) (E-18) (AMN-03) GWI-5 96% (reaction times were adapted) H-75

2-Methyl-N-[(1R)-6-(3-pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-4- (trifluoromethyloxy)-benzamide (H-75) (E-18) (AMN-33) GWI-5 79% H-76

2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-6-(trifluoromethyl)- benzamide (H-76) (E-19) (AMN-03) GWI-5 87% H-77

2-Chloro-N-[(4R)-8-fluoro-6-(3-pyridin- 4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)- 3,4-dihydro-2H-chromen-4-yl]-benzamide (H-77) (E-17) (AMN-33) GWI-5 55% H-78

2-Chloro-N-[(4R)-8-fluoro-6-(9-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-3-carbonyl)- 3,4-dihydro-2H-chromen-4-yl]-benzamide (H-78) (E-17) (AMN-01) GWI-5 87% H-79

2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.4]nonane-3-carbonyl)-1,2,3,4- tetrahydro-naphthalen-1-yl]-benzamide (H- 79) (E-06) (AMN-02) GWI-5 73% H-80

2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8- diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-80) (E-06) (AMN-07) GWI-5 85% H-81

2-Chloro-N-[(1R)-7-(7-pyridin-4-yl-3,7- diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4- tetrahydro-naphthalen-1-yl]-benzamide (H- 81) (E-06) (AMN-15) GWI-5 71% H-82

2-Chloro-N-[(1R)-6-fluoro-7-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-82) (E-20) (AMN-03) GWI-5 76% H-83

2-Chloro-N-[(1R)-6-(3-pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-6-(trifluoromethyl)- benzamide (H-83) (E-19) (AMN-33) GWI-5 83% H-84

N-[(1R)-6-(8-Pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-pyrimidine-5- carboxylic acid amide (H-84) (E-21) (AMN-03) GWI-5 59% H-85

2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-6-(trifluoromethyl)- benzamide (H-85) (E-19) (AMN-01) GWI-5 80% (reaction times were adapted) H-86

N-[(1R)-6-(3-Pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-pyrimidine-5- carboxylic acid amide (H-86) (E-21) (AMN-33) GWI-5 12% (reaction times were adapted) H-87

2-Chloro-N-[(1R)-6-fluoro-7-(3-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-8-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-87) (E-20) (AMN-33) GWI-5 76% H-88

2-Chloro-N-[(1R)-6-fluoro-7-(9-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-88) (E-20) (AMN-01) GWI-5 80% H-89

2-Chloro-N-[(1R)-5-fluoro-6-(3-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-89) (E-15) (AMN-33) GWI-5 80% H-90

2-Chloro-N-[(1R)-5-fluoro-6-(9-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-90) (E-15) (AMN-01) GWI-5 78% H-91

2-Chloro-N-[(1R)-6-(3-pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-91) (E-03) (AMN-33) GWI-5 61% (reaction times were adapted) H-92

2-Chloro-N-[(4R)-7-fluoro-6-(9-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-3-carbonyl)- 3,4-dihydro-2H-chromen-4-yl]-benzamide (H-92) (E-16) (AMN-01) GWI-5 19% H-93

2-Chloro-N-[(1R)-5-methyl-6-(8-pyridin- 4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-93) (E-12) (AMN-03) GWI-5 79% H-94

2,3-Dichloro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-94) (E-22) (AMN-03) GWI-5 >99%  H-95

2,3-Dichloro-N-[(1R)-6-(9-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-95) (E-22) (AMN-01) GWI-5 93% H-96

7-Chloro-2-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-96) (G-07) (AMN-03) GWI-5 83% H-97

2-Chloro-N-[(1R)-6-[9-(5,6,7,8-tetra- hydro-[1,2,4]triazolo[1,5-a]pyrazine-7- carbonyl)-3-azaspiro[5.5]undecane- 3-carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-97) (E-03) (AMN-35) GWI-5 70% H-98

2,5-Dichloro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-98) (E-24) (AMN-03) GWI-5 67% H-99

2,6-Dichloro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-99) (E-25) (AMN-03) GWI-5 74% H-100

2,6-Dichloro-N-[(1R)-6-(9-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-100) (E-25) (AMN-01) GWI-5 83% H-101

2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-101) (E-26) (AMN-03) GWI-5 84% H-102

2-Fluoro-N-[(1R)-6-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-102) (E-26) (AMN-01) GWI-5 41% H-103

4-Methoxy-2,5-dimethyl-N-[(1R)-6-(8- pyridin-4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-103) (E-27) (AMN-03) GWI-5 94% (reaction times were adapted) H-104

2,6-Dimethyl-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-104) (E-28) (AMN-03) GWI-5 91% H-105

2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-105) (F-04) (AMN-03) GWI-5 55% H-106

2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4- tetrahydro-naphthalen-1-yl]- benzenesulfonic acid amide (H-106) (F-05) (AMN-03) GWI-5 55% H-107

2-Chloro-N-[(4R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-7- (trifluoromethyl)-3,4-dihydro-2H-chromen- 4-yl]-benzamide (H-107) (E-29) (AMN-03) GWI-5 84% H-108

2-Fluoro-4-methoxy-N-[(1R)-6-(8-pyridin- 4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-108) (E-30) (AMN-03) GWI-5 83% H-109

2-Chloro-6-fluoro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-109) (E-30) (AMN-03) GWI-5 63% H-110

2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-6-(trifluoromethyl)- benzamide (H-110) (E-31) (AMN-03) GWI-5 95% H-111

2-Chloro-N-[(1R)-6-[8-(2,6-dimethyl- pyridin-4-yl)-3,8-diazaspiro[4.5]decane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide hydrochloride (H-111) (E-03) (AMN-36) GWI-5 56% corresponding HCl-salt was precipitated H-112

2-Chloro-N-[(1R)-6-[8-(2-methyl-pyridin-4- yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]- 2,3-dihydro-1H-inden-1-yl]-benzamide (H- 112) (E-03) (AMN-37) GWI-5 71% H-113

2,3-Dichloro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-113) (F-06) (AMN-03) GWI-5 79% H-114

2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-pyridine-3- carboxylic acid amide (H-114) (E-32) (AMN-03) GWI-5 49% H-115

N-[(1R)-6-(8-Pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-4-(trifluoromethyl)- pyridine-3-carboxylic acid amide (H-115) (E-33) (AMN-03) GWI-5 87% H-116

2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-116) (F-07) (AMN-03) GWI-5 >99%  H-117

2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-117) (F-08) (AMN-03) GWI-5 57% (reaction times were adapted) H-118

N-[(1R)-6-(8-Pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2-(trifluoromethyl)- benzenesulfonic acid amide (H-118) (F-09) (AMN-03) GWI-5 88% H-119

2,6-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-119) (F-10) (AMN-03) GWI-5 >99%  (reaction times were adapted) H-120

2-Chloro-N-[6-[9-[2-(1H-imidazol-1-yl)- ethoxy]-3-azaspiro[5.5]undecane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-120) (E-01) (AMN-38) GWI-6 23% HATU (1.0 equiv.), DIPEA (3 equiv.) H-128

2-Chloro-N-[6-(8-hydroxy-8-pyridin-4-yl-3- azaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-128) (E-01) (AMN-39) GWI-6 20% (0.283 mmol) HATU (1.2 equiv.), DIPEA (3 equiv.) H-129

2-Chloro-N-[6-[8-(1-oxido-pyridin-1-ium-4- yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]- 2,3-dihydro-1H-inden-1-yl]-benzamide (H- 129) see below H-130

2-Chloro-N-[6-[8-[5-(trifluoromethyl)- pyrimidin-2-yl]-3,8-diazaspiro[4.5]decane- 3-carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-130) (E-01) (AMN-41) GWI-6 25% (0.19 mmol) HATU (1.1 equiv.), DIPEA (5 equiv.) H-131

2-Chloro-N-[6-[9-(1H-imidazol-1-yl)-3- azaspiro[5.5]undecane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-131) (E-01) (AMN-42) GWI-6 16% (0.55 mmol) HATU (1.0 equiv.), DIPEA (2 equiv.) H-132

2-Chloro-N-[3,3-dimethyl-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2- dihydro-inden-1-yl]-benzamide (H-132) (E-39) (AMN-03) GWI-6 44% (0.34 mmol) H-133

2-Chloro-N-[6-(8-pyridin-4-yl-3- azaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-133) (E-01) (AMN-43) GWI-6 24% (0.193 mmol) HATU (1.2 equiv.), DIPEA (3 equiv.) H-134

5-Methyl-2-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-1,2-dihydro- pyrrolo[2,1-e]imidazol-3-one (H-134) (G-06) (AMN-03) GWI-6 55% (0.185 mmol) HATU (1.1 equiv.), DIPEA (5 equiv.) H-135

2-Chloro-N-[(1R)-6-(8-pyridin-3-yl-3- azaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-135) (E-03) (AMN-44) GWI-6 25% (0.196 mmol) HATU (1.2 equiv.), DIPEA (3 equiv.) H-136

2-Chloro-N-methyl-N-[(1R)-6-(8-pyridin-4- yl-3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]- benzenesulfonic acid amide (H-136) (F-16) (AMN-03) GWI-7 31% (0.739 mmol) H-137

2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-N-(2,2,2-trifluoro- ethyl)-benzamide (H-137) (E-41) (AMN-03) GWI-7 22% (0.25 mmol) (instead of HOBt HOAt (1.5 equiv.)) H-138

2-Chloro-N-[6-(3-pyridin-4-yl-3,10- diazaspiro[5.6]dodecane-10-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-138) (E-01) (AMN-45) GWI-6 21% (0.147 mmol). HATU (1.1 equiv.), DIPEA (4 equiv.) H-139

2-Chloro-N-[(1R)-6-[8-(4-methoxyphenyl)- 3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-139) (E03) (AMN-47) GWI-6 58% (0.333 mmol) HATU (1.2 equiv.), DIPEA (5 equiv.) H-140

2-Chloro-N-[(1R)-6-[8-(4-cyano-phenyl)- 3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-140) (E03) (AMN-46) GWI-6 58% (0.59 mmol) HATU (1.0 equiv.), DIPEA (3 equiv.) H-141

2-Chloro-5-fluoro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-141) (E-42) (AMN-03) GWI-5 72% H-142

2,5-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-142) (F-11) (AMN-03) GWI-5 96% H-143

3-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-butyramide (H-143) (E-43) (AMN-03) GWI-5 74% H-144

4-Methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2-(trifluoromethyl)- benzenesulfonic acid amide (H-144) (F-12) (AMN-03) GWI-5 59% H-145

2-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4- yl-3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-propionamide (H-145) (E-44) (AMN-03) GWI-5 87% (reaction times were adapted) H-146

2-(2-Chlorophenyl)-2-methyl-N-[(1R)-6-(8- pyridin-4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- propionamide (H-146) (E-45) (AMN-03) GWI-5 70% H-147

4-Methoxy-2-methyl-N-[(1R)-6-(8-pyridin- 4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzenesulfonic acid amide (H-147) (F-13) (AMN-03) GWI-5 20% H-148

1-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4- yl-3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-cyclopropane- 1-carboxylic acid amide (H-148) (E-46) (AMN-03) GWI-5 70% H-149

2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-6-(trifluoromethyl)- benzenesulfonic acid amide (H-149) (F-14) (AMN-03) GWI-5 75% H-150

1-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4- yl-3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]- methanesulfonic acid amide (H-150) (F-15) (AMN-03) GWI-5 86% H-151

2-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4- yl-3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-acetamide (H- 151) (E-47) (AMN-03) GWI-5 87% H-152

2-(2-Fluorophenyl)-N-[(1R)-6-(8-pyridin-4- yl-3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-acetamide (H- 152) (E-48) (AMN-03) GWI-5 76% H-153

2-Chloro-3-fluoro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-153) (E-49) (AMN-03) GWI-5 83% H-154

2-(o-Tolyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-acetamide (H-154) (E-50) (AMN-03) GWI-5 74% H-155

7-Chloro-2-[(1S)-5-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-155) (E-51) (AMN-03) GWI-5 80% H-156

2-Chloro-N-[(1S)-5-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-156) (E-51) (AMN-01) GWI-5 89% H-157

2-Chloro-N-[(1S)-5-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-157) (G-08) (AMN-03) GWI-5 50% H-158

7-Chloro-2-[(1S)-5-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-158) (G-08) (AMN-01) GWI-5 48% H-159

7-Chloro-2-[(1R)-5-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-159) (G-09) (AMN-01) GWI-5 76% H-160

7-Chloro-2-[(1R)-5-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-160) (G-09) (AMN-03) GWI-5 72% H-161

2-Chloro-N-[(1S)-4-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-161) (E-52) (AMN-03) GWI-5 >99%  H-162

2-Chloro-N-[(1R)-4-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-162) (E-53) (AMN-03) GWI-5 98% H-163

2-Chloro-N-[(1S)-4-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-163) (E-52) (AMN-01) GWI-5 83% H-164

2-Chloro-N-[(1R)-4-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-164) (E-53) (AMN-01) GWI-5 84% H-165

2-Chloro-N-[(1S)-4-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-165) (F-17) (AMN-03) GWI-5 >99%  H-166

2-Chloro-N-[(1R)-4-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-166) (F-18) (AMN-03) GWI-5 88% H-167

2-Chloro-N-[(1R)-4-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-167) (F-18) (AMN-01) GWI-5 68% H-168

7-Chloro-2-[(1S)-4-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-168) (G-11) (AMN-03) GWI-5 76% H-169

7-Chloro-2-[(1R)-4-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-169) (G-10) (AMN-03) GWI-5 >99%  H-170

7-Chloro-2-[(1R)-4-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-170) (G-10) (AMN-01) GWI-5 32% H-171

2-Chloro-N-[(1R)-5-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-171) (E-54) (AMN-03) GWI-5 74% H-172

2-Chloro-N-[(1R)-5-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-172) (E-54) (AMN-01) GWI-5 84% H-173

2-Chloro-N-[(1R)-5-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-173) (F-19) (AMN-03) GWI-5 93% Notes: Typical reaction scale 0.15-0.7 mmol.

Synthesis of the Individual Substance h-49 2-Chloro-N-methyl-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide (H-49)

(I) LiHMDS (0.72 mmol, 1.5 eq., 1 M solution in THF) was added dropwise to a cooled (0° C.) solution of compound (H-05) (0.486 mmol, 1 eq.) in THF. The reaction mixture was stirred for min and MeI (0.534 mmol, 1.1 eq.) was then added at 0° C. The mixture was stirred at 25° C. for 3 h. The reaction mixture was quenched with water (5 ml) and extracted with methylene chloride (3×25 ml). The organic phase was washed successively with NH₄Cl solution (15 ml), water (15 ml) and sat. NaCl solution (15 ml) and dried over sodium sulfate. The solvent was concentrated on a rotary evaporator and the crude product was purified by column chromatography (silica gel, 3% methanol in methylene chloride) in order to obtain the desired product (H-49). Yield: 46%

Synthesis of the individual substance H-54 2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-2,9-diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide (H-54)

Step 1: (R)-tert-Butyl 2-(3-(2-chlorobenzamido)-2,3-dihydro-1H-indene-5-carbonyl)-2,9-diazaspiro[5.5]undecane-9-carboxylate

N-Ethyl-diisopropylamine (4 eq.) was added to a solution of (3R)-3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (E-03) (0.952 mmol, 1 eq.) in methylene chloride (18 ml). The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before tert-butyl 2,9-diazaspiro[5.5]undecane-9-carboxylate (1.1 eq.) was added. The reaction mixture was stirred at room temperature for 2.5 d. Then, the reaction mixture was washed in each case 1× with 10% NH₄Cl solution, sat. NaHCO₃ solution and sat. NaCl solution. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica; ethyl acetate/hexane/ammonia (25% aq.) 70:10:0.8). Yield: 70%

Step 2: (R)—N-(6-(2,9-Diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)-2-chlorobenzamide hydrochloride

Acetyl chloride (5 eq.) was added to an ice-cold solution of (R)-tert-butyl 2-(3-(2-chlorobenzamido)-2,3-dihydro-1H-indene-5-carbonyl)-2,9-diazaspiro[5.5]undecane-9-carboxylate (0.652 mmol, 1 eq.) in ethanol. The reaction mixture was then stirred at room temperature overnight. The solvent was concentrated in vacuo and the residue was dissolved in ethanol/acetone (1:3, 5 ml) and diethyl ether (100 ml) was added. The white solid was filtered out, washed with diethyl ether and dried in vacuo. Yield: 82%

Step 3: 2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-2,9-diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide (H-54)

A mixture of (R)—N-(6-(2,9-diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)-2-chlorobenzamide hydrochloride (0.491 mmol, 1.0 eq.), triethylamine (5.0 eq.) and 4-chloropyridine hydrochloride (3.0 eq.) in n-butanol (13 ml) was stirred at 110° C. overnight. Ethyl acetate and sat. NaHCO₃ solution were added and the aqueous phase was extracted with ethyl acetate a further 4×. The combined organic phases were washed 1× with sat. NaCl solution, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica, ethyl acetate/ethanol/ammonia (25% aq) 100:10:1) to obtain the desired product (H-54). Yield: 73%

Synthesis of the individual substance H-129 2-Chloro-N-[6-[8-(1-oxido-pyridin-1-ium-4-yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide (H-129)

Step-1: tert-Butyl 8-(2,2,2-trifluoroacetyl)-2,8-diazaspiro[4.5]decane-2-carboxylate

To a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (600 mg, 2.5 mmol, 1 eq.) in MC (25 ml) DIPEA was added, the mixture stirred for 5-10 min and then TFAA (2.6 g, 12.5 mmol, 5 eq.) was added at 0° C. The reaction mixture was stirred at 25° C. for 2.5 h. The mixture was then diluted with MC (200 ml) and washed with water (2×100 ml) and brine (100 ml). The organic layer was dried over Na₂SO₄, filtered and evaporated to dryness to yield a yellowish oil. The crude product was used in the next step without further purification.

Step-2: 2,2,2-Trifluoro-1-(2,8-diazaspiro[4.5]decan-8-yl)ethanone

TFA (1 ml) was added to a stirred solution of tert-butyl 8-(2,2,2-trifluoroacetyl)-2,8-diazaspiro[4.5]decane-2-carboxylate (840 mg, 2.5 mmol) in MC (4 ml) and the mixture was stirred at RT for 12 h. The reaction mixture was then concentrated under reduced pressure and azeotroped with MC (2×10 ml). The crude product was dried and used for the next step without further purification.

Step-3: 2-Chloro-N-(6-(8-(2,2,2-trifluoroacetyl)-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)benzamide

To a suspension of 3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (E-01) (789 mg, 2.49 mmol, 1.0 eq.) in THF (20 ml) was added HATU (1.04 g, 2.76 mmol, 1.1 equiv.) and DIPEA (2.1 ml, 12.4 mmol, 5 eq.) at 0° C. and the reaction mixture was allowed to stir for 15 min. A solution of 2,2,2-trifluoro-1-(2,8-diazaspiro[4.5]decan-8-yl)ethanone (587 mg, 2.49 mmol, 1.0 equiv.) in THF (5 ml) was then added and the reaction mixture was stirred at 25° C. for 15 h. The mixture was diluted with MC (300 ml) and washed successively with sodium bicarbonate solution (40 ml), ammonium chloride solution (50 ml), water (50 ml) and brine (50 ml). The organic layer was dried over sodium sulfate and the solvent evaporated under reduced pressure to obtain the crude material which was purified by column chromatography (silica gel; 0-3% methanol/MC) to yield the pure final product as a white solid. Yield: 72% (1 g, 1.8 mmol).

Step-4: N-(6-(2,8-Diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)-2-chlorobenzamide

2 M KOH solution (4 ml) was added to a stirred solution of 2-chloro-N-(6-(8-(2,2,2-trifluoroacetyl)-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)benzamide (200 mg, 0.374 mmol, 1 eq.) in MeOH (4 ml) and the mixture was stirred for 5 h. Methanol was removed under reduced pressure and it was diluted with EtOAc (100 ml) and washed with water (10 ml) and brine (20 ml). The organic layer was dried over sodium sulfate, filtered and concentrated to dryness. The crude material was used for the next step without further purification.

Step-5: 2-Chloro-N-[6-[8-(1-oxido-pyridin-1-ium-4-yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide (H-129)

A stirred mixture of N-(6-(2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)-2-chlorobenzamide (350 mg, 0.799 mmol, 1 eq.), DIPEA (0.34 ml, 1.99 mmol, 2.5 eq.) and 4-chloropyridine (103 mg, 0.799 mmol, 1 eq.) in EtOH (7 ml) was heated at 130° C. for 72 h. The solvent was removed and the crude material was purified by column chromatography (silica gel, 3-5% MeOH/MC) to afford the final product as a light brown solid. Yield: 23% (100 mg, 0.19 mmol).

Analytical Data: Materials and Methods for HPLC-MS Analytics:

HPLC: Waters Alliance 2795 with PDA Waters 2998; MS: Micromass Quattro Micro™ API; Column: Waters Atlantis® T3, 3 μm, 100 Å, 2.1×30 mm; Col. temp.: 40° C., Eluent A: purified water+0.1% formic acid; Eluent B: acetonitrile (gradient grade)+0.1% formic acid; Gradient: 0% B to 100% B in 8.8 min, 100% B for 0.4 min, 100% B to 0% B in 0.01 min, 0% B for 0.8 min; Flow: 1.0 mL/min; Ionisation: ES+, 25 V; make up: 100 μL/min 70% methanol+0.2% formic acid; UV: 200-400 nm.

Example no. [M+] found R.t. [min] H-01 541.2 3.0 min H-02 515.2 1.56 min  H-03 589.3 3.4 min H-04 501.1 2.7 min H-05 515.1 2.7 min H-06 506.3 2.9 min H-07 542.2 2.9 min H-08 544.2 3.2 min H-09 543.4 4.4 min H-10 543.4 4.5 min H-11 529.3 3.0 min H-12 529.3 3.0 min H-13 541.3 3.2 min H-14 555.3 3.3 min H-15 541.3 3.2 min H-16 589.3 3.6 min H-17 603.3 3.8 min H-18 589.3 3.5 min H-19 603.3 3.7 min H-20 515.3 2.8 min H-21 515.3 2.8 min H-22 529.3 3.0 min H-23 515.3 2.9 min H-24 529.3 3.0 min H-25 515.3 2.9 min H-26 529.3 3.1 min H-27 501.3 2.8 min H-28 549.4 2.1 min H-29 577.4 2.9 min H-31 563.5 2.1 min H-32 563.47 2.11 min  H-33 488.3 2.7 min H-34 515.3 2.9 min H-35 515.3 2.9 min H-36 591.5 2.5 min H-37 548.4 4.1 min H-38 549.4 2.7 min H-39 515.3 2.9 min H-40 548.3 4.5 min H-41 532.3 3.5 min H-42 582.3 5.2 min H-43 515.3 2.8 min H-44 516.3 3.7 min H-45 583.3 3.6 min H-46 633.3 3.6 min H-47 543.4 3.3 min H-48 583.3 4.5 min H-49 529.3 3.0 min H-50 565.3 3.4 min H-51 584.3 4.3 min H-52 603.6 3.0 min H-53 495.4 2.9 min H-54 529.4 3.1 min H-55 573.4 2.9 min H-56 561.4 3.2 min H-57 531.4 2.8 min H-58 545.4 2.9 min H-59 529.4 3.1 min H-60 545.4 3.1 min H-61 525.4 2.9 min H-62 603.5 3.1 min H-63 545.4 3.0 min H-64 533.4 2.9 min H-65 549.4 2.8 min H-66 543.4 3.2 min H-67 531.4 2.7 min H-68 561.4 3.4 min H-69 543.4 3.1 min H-70 529.4 2.9 min H-71 515.4 2.9 min H-72 529.4 3.1 min H-73 549.4 2.8 min H-74 579.5 3.4 min H-75 579.4 3.6 min H-76 583.4 3.0 min H-77 549.4 2.8 min H-78 563.4 3.0 min H-79 515.4 2.9 min H-80 543.4 3.2 min H-81 529.4 3.0 min H-82 547.4 3.1 min H-83 583.4 3.1 min H-84 483.4 2.5 min H-85 597.4 3.2 min H-86 483.4 2.5 min H-87 547.4 3.1 min H-88 561.4 3.3 min H-89 533.4 2.9 min H-90 547.4 3.0 min H-91 515.4 2.9 min H-92 563.4 2.9 min H-93 529.4 3.0 min H-94 549.3 3.1 min H-95 563.4 3.3 min H-96 527.4 3.1 min H-97 601.1 3.5 min H-98 549.1 3.0 min H-99 549.1 2.9 min H-100 563.1 3.1 min H-101 499.2 2.9 min H-102 513.2 3.1 min H-103 539.2 3.2 min H-104 509.1 2.9 min H-105 551.0 3.1 min H-106 565.0 3.2 min H-107 599.0 3.1 min H-108 529.1 3.0 min H-109 533.0 2.8 min H-110 567.0 3.0 min H-111 543.1 3.1 min H-112 529.1 2.9 min H-113 585.0 3.39 min  H-114 496.1 2.20 min  H-115 550.08 2.63 min  H-116 535.04 2.9 min H-117 531.07 3.07 min  H-118 585.0 3.1 min H-119 584.9 3.1 min H-120 561.4 3.2 min H-128 530.4 2.6 min H-129 531.4 3.0 min H-130 584.4 4.6 min H-131 517.4 2.8 min H-132 543.4 3.2 min H-133 514.4 3.0 min H-134 496.1 3.1 min H-135 514.1 2.9 min H-136 565.0 3.5 min H-137 596.9 3.4 min H-138 543.0 3.0 min H-139 544.0 2.8 min H-140 539.0 4.1 min H-141 533.0 2.8 min H-142 584.9 3.3 min H-143 461.1 2.6 min H-144 614.9 3.3 min H-145 543.0 3.2 min H-146 557.0 3.1 min H-147 561.0 3.1 min H-148 555.0 3.2 min H-149 618.9 3.0 min H-150 564.9 3.1 min H-151 529.0 2.9 min H-152 513.1 2.7 min H-153 533.0 2.8 min H-154 509.1 2.9 min H-155 515.4 2.9 min H-156 529.4 3.1 min H-157 527.4 3.1 min H-158 541.4 3.2 min H-159 541.0 3.3 min H-160 527.0 3.1 min H-161 515.1 2.7 min H-162 515.1 2.7 min H-163 529.1 2.9 min H-164 529.1 3.0 min H-165 551.0 2.9 min H-166 551.0 3.0 min H-167 565.0 3.1 min H-168 527.1 3.1 min H-169 527.1 3.0 min H-170 541.1 3.2 min H-171 515.1 2.8 min H-172 529.1 3.0 min H-173 551.01 3.15 min 

D. Parallel Synthesis Library No. 1: 1) Intermediate Syntheses Synthesis of: 3,9-Diazaspiro[5.5]undecane-9-carboxylic acid tert-butyl ester

Step 1: A mixture of 1-benzyl-piperidin-4-one (100 g, 0.53 mol) and ethyl cyanoacetate (119.4 g, 1.06 mol) was added dropwise to an ethanolic ammonia solution (9 M, 420 ml) at −10° C. by means of a dropping funnel and the solution was stored in a refrigerator for 2 days. The yellow solid which had precipitated out was filtered out and washed with hexane (200 ml). Water (960 ml) was added to the dried solid (100 g) and the boiling suspension was acidified with 2 N HCl (200 ml). The solution obtained was cooled to room temperature in order to obtain a yellow precipitate, which was filtered out in order to obtain the desired product in the crude state.

Yield: 47% (80 g)

Step 2: The product just obtained in step 1 (22 g, 68.32 mmol) and 65% sulfuric acid (45 ml) were refluxed in a round-bottomed flask for 2 h. The reaction mixture was cooled to room temperature, 27.5 ml of water were added and the mixture was refluxed for a further 14 h. The reaction mixture was then cooled to room temperature and adjusted to pH=10 with 40% NaOH solution, before it was acidified with 2 N HCl (˜110 ml). The solvent was concentrated under reduced pressure and the residue was co-distilled with benzene (350 ml) in a Dean-Stark apparatus. Finally, benzene was distilled off, the residue was taken up in ethanol (350 ml) and the reaction mixture was refluxed for 18 h. The course of the reaction was monitored by means of TLC (50% ethyl acetate in hexane, R_(f)=0.3). When the reaction was complete, the reaction mixture was filtered over a sinter funnel and the filtrate was cooled to 0-5° C. and neutralized with sodium carbonate (72 g). The ethanol was concentrated under reduced pressure and the residue was taken up in ethyl acetate (700 ml). The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated . . . reduced pressure. The crude product was purified by column chromatography.

Yield: 65% (15 g)

Step 3: A solution of the product just obtained in step 2 (21 g, 60.5 mmol) in THF (472 ml) was added to a stirred suspension of lithium aluminium hydride (3.4 g, 90.7 mmol) in THF (105 ml) at −5 to 0° C. The reaction mixture was stirred at room temperature for 12 h, subsequently cooled to −5 to 0° C. and worked up by the Fischer method [slowly add i) 3.5 ml of water diluted with 11.5 ml of THF ii) 3.5 ml of a 10% NaOH solution iii) 3.5 ml of water]. The reaction mixture was filtered over Celite and washed (twice) with THF. The organic phase was concentrated in order to obtain the crude product.

Yield: 88% (14 g)

Step 4: The product just obtained in step 3 (57 g, 216.7 mmol) was dissolved in methanol (570 ml) in a 2 l Parr hydrogenation vessel, Boc anhydride (61.4 g, 281.7 mmol) and palladium-on-carbon (5.7 g, 10% Pd) were added under an N₂ atmosphere and hydrogenation was carried out for 12 h under 50 psi. The reaction mixture was filtered over Celite and washed with methanol (3×150 ml). The organic phase was concentrated in order to obtain the crude product as a yellow, tacky mass. The crude product was purified by column chromatography.

Yield: 78% (46 g)

Step 5: Triethylamine (72.5 ml, 580 mmol) was added at −20° C. to a solution of the product just obtained in step 4 (49 g, 179 mmol) in methylene chloride (1 l), followed by methanesulfonyl chloride (46.2 g, 403 mmol). The reaction mixture was stirred at −20° C. for 30 min, water was added and the organic phase was separated off, after the mixture had . . . stirred for 20 min. The aqueous phase was extracted with methylene chloride (3×150 ml). The combined organic phases were dried over sodium sulfate and concentrated in order to obtain the crude product. The crude product was purified by column chromatography.

Yield: 89% (50 g)

Step 6: The product just obtained in step 5 (70 g; 163 mmol) and benzylamine (105 ml, 962 mmol) were heated at 75° C. in a 500 ml round-bottomed flask for 2 h. The reaction mixture was cooled to 0° C. and adjusted to pH ˜10 with 2% NaOH solution. Water (1,500 ml) was then added and the mixture was extracted with ethyl acetate (3×500 ml). The organic phase was washed with sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 80% (75 g)

Step 7: Palladium-on-charcoal (2.7 g, 10% Pd/C) was added under an N₂ atmosphere to a solution of the product just obtained in step 6 (27 g, 78.488 mmol) in methanol (270 ml) and acetic acid (27 ml). Hydrogenation was carried out under a hydrogen pressure of 50 psi in a Parr apparatus for 16 h. The reaction mixture was filtered over Celite, washed with methanol (3×100 ml) and concentrated. The residue was rendered basic with 10% sodium carbonate solution and the mixture was extracted with methylene chloride (3×250 ml). The combined organic phases were dried over sodium sulfate and concentrated. The crude product was purified by column chromatography.

Yield: 90% (18 g)

Synthesis of: 3-(tert-Butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid

3-(tert-Butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (821 g, 0.072 mol, cf. Synthesis of amino acid ester A-01) was dissolved in 110 ml of a THF-methanol-water mixture (6:4:1). The reaction mixture was cooled to 0° C., lithium hydroxide monohydrate (13.6 g, 0.32 mol) was added in portions and the mixture was stirred at room temperature for 8 h. The reaction mixture was concentrated to dryness, the residue was dissolved in a minimum of water and the solution was washed with ether. The aqueous phase was cooled to 0° C. and acidified slowly with 10% citric acid solution. The white solid which had precipitated out was filtered out, washed with water and dried in vacuo at 60° C. for 24 h in order to obtain the pure acid compound as a cream-coloured solid.

Yield: 77% (15 g)

2) Synthesis of the Amine Units (AMN_CC): Overview:

AMN-CC unit no. Structure AMN-CC name AMN_CC-01

N-[6-(3-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-9-carbonyl)-2,3- dihydro-1H-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-01) AMN_CC-02

N-methyl-N-[6-(3-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-9-carbonyl)-2,3- dihydro-1H-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-02) AMN_CC-03

N-[6-[3-[4-(trifluoromethyl)-phenyl]-3,9- diazaspiro[5.5]undecane-9-carbonyl]-2,3- dihydro-1H-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-03) AMN_CC-04

N-[6-(2-pyridin-4-yl-2,8- diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-04) AMN_CC-13

N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-1,2- dihydro-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-13) AMN_CC-14

N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-1,3- dihydro-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-14) AMN_CC-15

N-[6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-15)

Synthesis of Amine (AMN_CC-01) N-[6-(3-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-2,3-dihydro-1H-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-01)

Step 1: 3,9-Diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (6 g, 23.6 mmol), 4-bromopyridine hydrochloride (4.58 g, 23.6 mmol) and sodium tert-butanolate (6.8 g, 70.8 mmol) were suspended in toluene and the suspension was then degassed under an argon atmosphere for 20 min. BINAP (293 mg, 0.47 mmol) and Pd(OAc)₂ (317 mg, 1.4 mmol) were added and the reaction mixture was first degassed for a further 20 min and then refluxed for 4 h. The reaction was monitored by TLC (MeOH): CH₂Cl₂=1:9, R_(f)=0.9), and after complete consumption of the starting material the reaction mixture was cooled to room temperature, diluted with ethyl acetate, stirred for 15 min and filtered over Celite. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 51% (4 g)

Step 2: Trifluoroacetic acid (7 ml) was added at 0° C. to a solution of the product just obtained (3 g, 9 mmol) in methylene chloride (70 ml) and the mixture was stirred at 23° C. for 16 h. The reaction mixture was then concentrated under reduced pressure in order to obtain the crude amine compound as the TFA salt. This was employed in the next step without further purification.

EDC.HCl (3.48 g, 18.1 mmol) and HOBT (2.45 g, 18.4 mmol) were added to a solution of 3-(tert-Butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid (3.35 g, 12.1 mmol) in THF (50 ml) and the mixture was cooled to 0° C. DIPEA (6.28 g, 8.98 ml, 48.4 mmol) was then added and the mixture was stirred for a further 10 min, before a solution of the amine TFA salt in THF (50 ml) was added dropwise to the reaction mixture and the mixture was stirred for 16 h.

For working up, water was added and the mixture was extracted with ethyl acetate (3×100 ml). The combined organic phases were washed with water and sat. NaCl solution and dried over sodium sulfate and concentrated. The crude product was purified by column chromatography.

Yield: 78% (3.5 g)

Synthesis of Amine (AMN_CC-02) N-Methyl-N-[6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-2,3-dihydro-1H-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-02)

Step 1: NaH (1.4 g, 30 mmol, 60% in mineral oil) was added in portions to a solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (3.4 g, 11.68 mmol) in DMF (60 ml) at 0° C. and the mixture was then stirred at room temperature for 2 h. The reaction mixture was cooled to 0° C., methyl iodide (2.19 ml, 30 mmol) was added and the mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with ice, diluted with water and extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCL solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 61.75%

Step 2: The product just obtained in step 1 (2 g, 6.55 mmol) was dissolved in 110 ml of a THF-methanol-water mixture (6:4:1). The reaction mixture was cooled to 0° C., lithium hydroxide monohydrate (1.31 g, 30 mmol) was added in portions and the mixture was stirred at room temperature for 8 h. The reaction mixture was concentrated to dryness, the residue was dissolved in a minimum of water and the solution was washed with ether. The aqueous phase was cooled to 0° C. and acidified slowly with dilute HCl solution. The white solid which had precipitated out was filtered out, washed with water and dried in vacuo at 60° C. for 24 h in order to obtain the pure acid compound as a cream-coloured solid.

Yield: 99%

Step 3: TFA (14 ml) was added to a stirred solution of 9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (5.9 g, 18.09 mmol) in methylene chloride (100 ml) at 0° C. and the reaction mixture was stirred at 23° C. for 16 h. The reaction mixture was concentrated in order to obtain the TFA salt, which was employed in the next step without further purification.

EDCI.HCl (6.91 g, 36 mmol) and HOBT (2.45 g, 18.4 mmol) were added to a solution of the acid obtained in step 2 (5.26 g, 18.09 mmol) in THF (50 ml) and the mixture was cooled to 0° C. DIPEA (6.28 g, 8.98 ml, 48.4 mmol) was then added to the reaction mixture and the mixture was stirred for 10 min. A solution of the TFA salt of the amine in THF (50 ml) was added dropwise to the reaction mixture and the mixture was stirred for 16 h. For working up, water was added and the mixture was extracted with ethyl acetate (3×100 ml). The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 31.57%

Synthesis of Amine (AMN_CC-03) N-[6-[3-[4-(Trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-9-carbonyl]-2,3-dihydro-1H-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-03)

Step 1: Sodium tert-butanolate (3 eq.) and 4-trifluoromethyl bromobenzene (1.2 eq.) were added to a toluene solution (5 ml/mmol) of 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (1 eq.) and the mixture was degassed under an argon atmosphere. (+/−)BINAP (0.06 eq.) and Pd(OAc)₂ (0.02 eq.) was then added and the mixture was refluxed for 2 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and washed successively with water and sat. NaCl solution. After drying over sodium sulfate, it was concentrated under reduced pressure. The crude product was purified by column chromatography (5% methanol in methylene chloride).

Yield: 51%

Step 2: TFA (80 ml) was added at 0° C. to a solution of the product just obtained in step 1 (4 g, mmol) in methylene chloride (320 ml) and the mixture was stirred at 23° C. for 2 h. The reaction mixture was concentrated in order to obtain the amine compound as the TFA salt, which was employed in the next step without further purification.

HATU (7.82 g, 20 mmol) was added to a solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid (2.85 g, 10 mmol) in methylene chloride (25 ml), the reaction the mixture was cooled to 0° C., DIPEA (6.15 g, 30 mmol) was added and the mixture was stirred for 10 min. A solution of the amine TFA salt in methylene chloride (25 ml) was added dropwise to the reaction mixture and the mixture was stirred for 16 h. For working up, water was added and the mixture was extracted with ethyl acetate (3×100 ml). The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 53%

Synthesis of Amine (AMN_CC-04) N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-04)

Step 1: Sodium tert-butanolate (3 eq.) and 4-bromopyridine hydrochloride (1.2 eq.) were added to a toluene solution (5 ml/mmol) of 2,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester (1 eq.) and the mixture was degassed under an argon atmosphere. (+/−)BINAP (0.06 eq.) and Pd(OAc)₂ (0.02 eq.) was then added and the mixture was refluxed for 2 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and washed successively with water and sat. NaCl solution. After drying over sodium sulfate, it was concentrated under reduced pressure. The crude product was purified by column chromatography (5% methanol in methylene chloride).

Yield: 53.08%

Step 2: TFA (90 ml) was added at 0° C. to a solution of the product just obtained in step 1 (4.5 g, 14.1 mmol) in methylene chloride (200 ml) and the mixture was stirred at 23° C. for 2 h. The reaction mixture was concentrated in order to obtain the amine compound as the TFA salt, which was employed in the next step without further purification.

HATU (10.8 g, 28.3 mmol) was added to a solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid (3.93 g, 14.19 mmol) in methylene chloride (100 ml), the reaction the mixture was cooled to 0° C., DIPEA (2.4 ml, 14 mmol) was added and the mixture was stirred for 10 min. A solution of the amine TFA salt and DIPEA (2.4 ml, 14 mmol) in methylene chloride (50 ml) was added dropwise to the reaction mixture and the mixture was stirred for 16 h. For working up, water was added and the mixture was extracted with ethyl acetate (3×100 ml). The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 78.76%

Synthesis of Amine (AMN_CC-13) N-[3,3-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-13)

Step 1: Bromine (0.6 g, 3.75 mmol) was added to a mixture of AlCl₃ (1.04 g, 7.8 mmol) and 3,3-dimethyl-indan-1-one (0.5 g, 3.1 mmol) at 100° C. and the mixture was kept at this temperature for 40-45 min. The reaction mixture was quenched with crushed ice and extracted with ethyl acetate (3×50 ml). The organic phase was separated off, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 26% (200 mg)

Step 2: Triethylamine was added to a solution of the product just obtained in step 1 (100 mg, 0.418 mmol) in a mixture of DMSO (5 ml) and methanol (4 ml) and the reaction mixture was degassed under an argon atmosphere for 15 min. Palladium acetate (4 mg, 0.02 mol) and dppp (1,3-bis-diphenylphosphino propane) (8 mg, 0.02 mol) were added and the mixture was degassed under a CO atmosphere for 30 min. The reaction mixture was stirred at 65° C. under a CO balloon pressure for 2 h. Methanol was removed under reduced pressure, the residue obtained was diluted with water and the mixture was extracted with diethyl ether. The organic phase was separated off, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 44% (40 mg)

Step 3: Hydroxylamine hydrochloride (3.4 g, 49.3 mol) and sodium acetate (8 g, 98.3 mol) were added to a solution of the ester just obtained (4.3 g, 19.7 mol) in methanol (75 ml) and the reaction mixture was heated at 80° C. for 2 h. The course of the reaction was monitored by means of TLC (30% ethyl acetate in hexane) and when the conversion of the reaction was complete the reaction mixture was concentrated and the residue was extracted with ethyl acetate. The organic phase was separated off, washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification.

Yield: 6 g crude

(IV) Zinc dust (6.6 g, 103 mmol) was added to an ethanolic solution (10 ml) of the product just obtained in step 3 (4 g, 17.1 mmol), water (10 ml) and conc. HCl (20 ml) and the mixture was refluxed for 2 h. It was then cooled to room temperature, filtered over Celite and concentrated in order to obtain the desired amine (6 g). The crude amine was dissolved in 1,4 dioxane (100 ml) and triethylamine (3.3 ml, 32.8 mmol), the solution was cooled to 5-10° C. and (Boc)₂O (6 g, 27.3 mmol) was added. This reaction mixture . . . stirred at room temperature for 12 h and then concentrated and the residue . . . taken up in ethyl acetate. The ethyl acetate phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated.

Yield: 51% (2.8 g)

Step 5: LiOH.H₂O (1.47 g, 35 mmol) was added to a solution of the product just obtained in step 4 (2.8 g, 8.75 mmol) in THF-MeOH—H₂O (55 ml, 6:4:1) and the mixture was stirred at room temperature for 12 h. The reaction mixture was then concentrated, the residue was dissolved in a minimum of water and the solution was washed with ether and acidified with 10% citric acid solution

The reaction mixture was extracted with ethyl acetate and the combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification.

Yield: 55% (1.5 g)

Step 6: EDCI.HCl (503 mg, 2.62 mmol), HOBT (177 mg, 1.311 mmol) and DIPEA (0.6 ml) were added to a solution of the product just obtained in step 5 (400 mg, 1.3114 mmol) in methylene chloride (10 ml). The reaction mixture was stirred at 25° C. for 30 min and then cooled to 0° C. and 3-pyridin-4-yl-3,9-diaza-spiro[5.5]undecane (364 mg, 1.57 mmol) was added. The reaction mixture was stirred at 25° C. for 12 h, subsequently diluted with methylene chloride and washed with sat. NH₄Cl solution and with NaHCO₃ solution. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 75% (500 mg)

Synthesis of Amine (AMN_CC-14) N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1.3-dihydro-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-14)

Step 1: A solution of 3-oxo-indane-5-carboxylic acid methyl ester (5 g, 26.3 mmol) in THF (40 ml) was added to a suspension of NaH (2.5 g, 2.2 eq.) in THF (25 ml) at 0° C. and the mixture was stirred at 0° C. for 15 min. Methyl iodide (9.9 ml, 184 mmol) was added and the reaction mixture was stirred at 20° C. for 4 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification.

Yield: 61% (3.5 g)

Step 2: Sodium acetate (28.28 g, 0.341 mol) and hydroxylamine hydrochloride (13.2 g, 0.191 mol) were added to a solution of the product just obtained in step 1 (14 g, 0.0736 mol) in methanol (100 ml). The reaction mixture was refluxed for 16 h and then concentrated under reduced pressure and the residue was diluted with ethyl acetate. The organic phase were washed with water, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification.

Yield: 60% (14 g)

Step 3: Water, more aqueous HCl (6 N, 5 ml) was added to a solution of the product just obtained in step 2 (1 g, 04.29 mmol) in ethanol (10 ml). Zinc powder (1.6 g, 25.75 mmol) was added in portions to the reaction mixture at 20° C. and the mixture was then stirred at 25° C. for 2 h. The reaction mixture was filtered and washing was carried out with methanol. The filtrate was first concentrated, the residue was then dissolved in 1,4-dioxane (50 ml) and triethylamine (3.5 ml) and Boc anhydride (34 ml, 159 mmol) were added at 0° C. The reaction mixture was stirred at 23° C. for 16 h and then concentrated under reduced pressure and the residue was diluted with ethyl acetate. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 73% (3 g)

Step 4: LiOH.H₂O (5.2 g, 125 mmol) was added in portions at 0° C. to a solution of the product just obtained in step 3 (10 g, 31.3 mmol) in a mixture of THF-methanol-water (110 ml, ratio 6:4:1) and the mixture was stirred at 20° C. for 12 h. The reaction mixture was concentrated to dryness under reduced pressure. The residue was dissolved in a minimum of water and the solution was washed with ether and acidified with 10% citric acid solution. The reaction mixture was extracted with ethyl acetate. The organic phase was washed with water and sat. sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification.

Yield: 55% (6 g)

Step 5: EDCI.HCl (939 mg, 4.9 mmol), HOBT (660 mg, 4.9 mmol) and DIPEA (2.2 ml, 12.69 mmol) were added to a solution of the product just obtained in step 4 (1 g, 3.2 mmol) in THF (20 ml). The reaction mixture was stirred at 25° C. for 30 min, a solution of 3-pyridin-4-yl-3,9-diaza-spiro[5.5]undecane (3.2 mmol, 1 eq.) in THF (20 ml) was then added and the mixture was stirred further at 25° C. for 12 h. The reaction mixture was diluted with methylene chloride and washed with sat. NH₄Cl solution and NaHCO₃ solution. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 70% (1.2 g)

Synthesis of Amine (AMN_CC-15) N-[6-(8-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-15)

Step 1: Sodium tert-butanolate (3 eq.) and 4-bromopyridine hydrochlorides (1.2 eq.) were added to a solution of the corresponding spiro-amine (7 g, 29.12 mmol) in toluene (145 mmol). The reaction mixture was degassed under an argon atmosphere, (+/−) BINAP (0.06 eq.) and Pd(OAc)₂ (0.02 eq.) were added and the mixture was refluxed for 2 h and finally cooled to room temperature.

The reaction mixture was diluted with ethyl acetate, washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 43.33%

Step 2: TFA (130 ml) was added at 0° C. to a solution of the product just obtained in step 1 (5.2 g, 16.40 mmol) in methylene chloride (200 ml) and the mixture was stirred at 23° C. for 16 h and finally concentrated under reduced pressure.

EDCI (6 g, 28.3 mmol) and HOBT (2.21 g, 16.40 . . . ) were added to a solution corresponding of the Boc-protected acid (4.54 g, 16.40 mmol) in methylene chloride (170 ml), the mixture was cooled to 0° C., DIPEA (11.4 ml, 64 mmol) was added and the mixture was stirred for a further min. A solution of the TFA salt of the amine and DIPEA (4 ml, 23 mmol) in methylene chloride (50 ml) was added dropwise to the reaction mixture and the mixture was stirred for 16 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate (3×100 ml).

The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 70.3%

3) Synthesis of the Acid Units, Acid Chlorides, Sulfonyl Chlorides and Isocyanates and aldehydes (ACI_CC, ACL_CC, SCI_CC, ICN_CC, ALD_CC):

Overview:

Unit no. Structure Unit name ACI_CC-01

pyridine-2-carboxylic acid ACI_CC-02

2-(trifluoromethyl)-benzoic acid ACI_CC-03

3-chloro-thiophene-2-carboxylic acid ACI_CC-04

5-chloro-thiophene-2-carboxylic acid ACI_CC-05

2,4-dichloro-benzoic acid ACI_CC-06

4-methoxy-2,6-dimethyl-benzoic acid ACI_CC-07

2-(chlorophenyl)-acetic acid ACI_CC-08

3-(chlorophenyl)-acrylic acid ACI_CC-09

2-(2-chlorophenyl)-2-phenyl-acetic acid SCI_CC-01

2-chloro-benzenesulfonyl chloride SCI_CC-02

4-methoxy-2,6-dimethyl-benzenesulfonyl chloride ICN_CC-01

1.2-Dichloro-4-isocyanato-benzene ICN_CC-02

1-Chloro-2-(isocyanato-methyl)-benzene

2-Chloro-benzoyl 2-Fluoro-benzoyl 2,6-Dichloro-benzoyl chloride (ACL_CC-01) chloride (ACL_CC-02) chloride (ACL_CC-03)

2-Methyl-benzoyl chloride 4-Cyano-benzoyl chloride 2-Fluoro-6-(trifluoromethyl)-benzoyl (ACL_CC-04) (ACL_CC-05) chloride (ACL_CC-06)

2,4-Difluoro-benzoyl chloride 4-Fluoro-2-(trifluoromethyl)-benzoyl Cyclohexanecarbonyl chloride (ACL_CC-07) chloride (ACL_CC-08) (ACL_CC-09)

3-Methyl-butyryl chloride Butyryl chloride 3-Cyclopentyl-propionyl chloride (ACL_CC-10) (ACL_CC-11) (ACL_CC-12)

Cyclopentanecarbonyl chloride Cyclobutanecarbonyl chloride Cyclopropanecarbonyl chloride (ACL_CC-13) (ACL_CC-14) (ACL_CC-15)

2-Methyl-butyryl chloride 2,6-Difluoro-benzoyl chloride 3,3-Dimethyl-butyryl chloride (ACL_CC-16) (ACL_CC- 17) (ACL_CC-18)

2-Methyl-propionyl chloride 2-Methylsulfanyl-pyridine-3- 2-tert-Butyl-5-methyl-2H-pyrazole-3- (ACL_CC-19) carbonyl chloride (ACL_CC-20) carbonyl chloride (ACL_CC-21)

5-tert-Butyl-2-methyl-2H-pyrazole-3- 2-Ethyl-butyryl chloride 2-(4-Chlorophenyl)-acetyl chloride carbonyl chloride (ACL_CC-22) (ACL_CC-23) (ACL_CC-24)

2,3-Dimethyl-benzoyl chloride 2,3-Dichloro-benzoyl chloride 2-Chloro-6-fluoro-benzoyl chloride (ACL_CC-25) (ACL_CC-26) (ACL_CC-27)

2-Chloro-4-fluoro-benzoyl Acetyl chloride 5-(Trifluoromethyl)-pyridine-2-carbonyl chloride (ACL_CC-28) (ACL_CC-29) chloride (ACL_CC-30)

2-Cyano-benzoyl chloride 2-Chloro-3-(trifluoromethyl)-benzoyl 2-Fluoro-4-methyl-benzoyl chloride (ACL_CC-31) chloride (ACL_CC-32) (ACL_CC-33)

2-Chloro-4,5-difluoro-benzoyl 2-Chloro-5-fluoro-benzoyl chloride 2-Chloro-5-(trifluoromethyl)-benzoyl chloride (ACL_CC-34) (ACL_CC-35) chloride (ACL_CC-36)

5-Chloro-2-(trifluoromethyl)-benzoyl Pyrazine-2-carbonyl chloride 2-Chloro-6-fluoro-3-methyl-benzoyl chloride (ACL_CC-37) (ACL_CC-38) chloride (ACL_CC-39)

2-Chloro-4-methoxy-benzoyl 2-Methyl-4-(trifluoromethyloxy)- 2,5-Dichloro-benzoyl chloride chloride (ACL_CC-40) benzoyl chloride (ACL_CC-41) (ACL_CC-42)

2-Chloro-6-(trifluoromethyl)- 2-Fluoro-4-methoxy-benzoyl 2,6-Dimethyl-benzoyl chloride benzoyl chloride (ACL_CC-43) chloride (ACL_CC-44) (ACL_CC-45)

Pyridine-2-carbaldehyde Pyridine-4-carbaldehyde 2-Chloro-4-fluoro-benzaldehyde (ALD_CC-01) (ALD_CC-02) (ALD_CC-03)

2-Chloro-6-fluoro-benzaldehyde 1-Methyl-1H-pyrrole-2- Cyclohexanecarbaldehyde (ALD_CC-04) carbaldehyde (ALD_CC-06) (ALD_CC-05)

Pyridine-3-carbaldehyde 4-Formyl-benzonitrile 2-Ethyl-butyraldehyde (ALD_CC-07) (ALD_CC-08) (ALD_CC-09)

2-Phenyl-acetaldehyde 3-Fluoro-4-methoxy-benzaldehyde 2,6-Difluoro-benzaldehyde (ALD_CC-10) (ALD_CC-11) (ALD_CC-12)

3,4-Difluoro-benzaldehyde 2,5-Difluoro-benzaldehyde 2-Fluoro-6-methoxy-benzaldehyde (ALD_CC-13) (ALD_CC-14) (ALD_CC-15)

1,3,5-Trimethyl-1H-pyrazole-4- 3,5-Dimethyl-isoxazole-4- [1,2,3]Thiadiazole-4-carbaldehyde carbaldehyde (ALD_CC-16) carbaldehyde (ALD_CC-17) (ALD_CC-18)

Quinoline-6-carbaldehyde Quinoxaline-6-carbaldehyde 3-Formyl-benzonitrile (ALD_CC-19) (ALD_CC-20) (ALD_CC-21)

2,4-Difluoro-benzaldehyde 2-Formyl-benzonitrile 1-Methyl-1H-benzotriazole-5- (ALD_CC-22) (ALD_CC-23) carbaldehyde (ALD_CC-24)

3-Methyl-3H-imidazole-4- 2-Methyl-propionaldehyde 1H-Imidazole-4-carbaldehyde carbaldehyde (ALD_CC-25) (ALD_CC-26) (ALD_CC-27)

5-Methyl-3H-imidazole-4- 1H-Pyrrole-2-carbaldehyde 2-Dimethylamino-pyrimidine-5- carbaldehyde (ALD_CC-28) (ALD_CC-29) carbaldehyde (ALD_CC-30)

1,5-Dimethyl-1H-pyrazole-4- 1-Ethyl-3-methyl-1H-pyrazole-4- 2-Methyl-1H-imidazole-4-carbaldehyde carbaldehyde (ALD_CC-31) carbaldehyde (ALD_CC-32) (ALD_CC-33)

3-(3-Fluorophenyl)-propionaldehyde 3-(4-Fluorophenyl)-propionaldehyde 3-Isocyanato-benzonitrile (ALD_CC-34) (ALD_CC-35) (ICN_CC-03)

(4-lsocyanato-phenyl)-dimethyl- 2,4-Difluoro-1-isocyanato-benzene 1,3-Dichloro-2-isocyanato-benzene amine (ICN_CC-04) (ICN_CC-05) (ICN_CC-06)

2,4-Dichloro-1-isocyanato- 4-Chloro-1-isocyanato-2- 2-Chloro-1-fluoro-4-isocyanato- benzene (ICN_CC-07) (trifluoromethyl)-benzene benzene (ICN_CC-08) (ICN_CC-09)

1-Isocyanato-propane Isocyanato-cyclohexane Isocyanato-methyl-benzene (ICN_CC-10) (ICN_CC-11) (ICN_CC-12)

1,2-Dichloro-4-(isocyanato-methyl)- 1,3-Difluoro-5-isocyanato- Propane-2-sulfonyl chloride benzene (ICN_CC-13) benzene (ICN_CC-14) (SCI_CC-03)

2-Cyano-benzenesulfonyl chloride 4-Fluoro-2-methyl-benzenesulfonyl 2-Chloro-benzenesulfonyl chloride (SCI_CC-04) chloride (SCI_CC-05) (SCI_CC-06)

2,4-Difluoro-benzenesulfonyl 5-Chloro-thiophene-2-sulfonyl 3-(Trifluoromethyl)-benzenesulfonyl chloride (SCI_CC-07) chloride (SCI_CC-08) chloride (SCI_CC-09)

2,5-Dichloro-benzenesulfonyl 2,4-Dichloro-benzenesulfonyl 2,6-Dichloro-benzenesulfonyl chloride chloride (SCI_CC-10) chloride (SCI_CC-11) (SCI_CC-12)

2,3-Dichloro-benzenesulfonyl 2,4,6-Trichloro-benzenesulfonyl 4-Bromo-2-chloro-benzenesulfonyl chloride (SCI_CC-13) chloride (SCI_CC-14) chloride (SCI_CC-15)

3-Cyano-4-fluoro-benzenesulfonyl 2,4,5-Trichloro-benzenesulfonyl [3-(Trifluoromethyl)phenyl]- chloride (SCI_CC-16) chloride (SCI_CC-17) methanesulfonyl chloride (SCI_CC-18)

(2-Fluorophenyl)-methanesulfonyl (3-Chlorophenyl)-methanesulfonyl 2-(2-Chlorophenyl)-ethanesulfonyl chloride (SCI_CC-19) chloride (SCI_CC-20) chloride (SCI_CC-21)

1-Methyl-1H-indole-4-sulfonyl 1-Methyl-1H-indole-5-sulfonyl chloride 2-Chloro-4-(trifluoromethyl)- chloride (SCI_CC-22) (SCI_CC-23) benzenesulfonyl chloride (SCI_CC-24)

2,6-Dichloro-4-(trifluoromethyl)- 2-Chloro-6-methyl-benzenesulfonyl [2-(Trifluoromethyl)-phenyl]- benzenesulfonyl chloride chloride (SCI_CC-26) methanesulfonyl chloride (SCI_CC-25) (SCI_CC-27)

4-Fluoro-2,6-dimethyl- benzenesulfonyl chloride (SCI_CC-28)

Carboxylic acid ACI_CC-01: Pyridine-2-carboxylic acid [CAS 4930-98-7] commercially obtainable from e.g. Acros. Carboxylic acid ACI_CC-02: 2-(Trifluoromethyl)-benzoic acid [CAS 433-97-6] commercially obtainable from e.g. Acros. Carboxylic acid ACI_CC-03: 3-Chloro-thiophene-2-carboxylic acid [CAS 59337-89-2] commercially obtainable from e.g. Acros. Carboxylic acid ACI_CC-04: 5-Chloro-thiophene-2-carboxylic acid [CAS 24065-33-6] commercially obtainable from e.g. Acros. Carboxylic acid ACI_CC-05: 2,4-Dichloro-benzoic acid [CAS 50-84-0] commercially obtainable from e.g. Acros. Carboxylic acid ACI_CC-06: 4-Methoxy-2,6-dimethyl-benzoic acid [CAS 37934-89-7] commercially obtainable from e.g. Transworldchemicals. Carboxylic acid ACI_CC-07: 2-(2-Chlorophenyl)-acetic acid [CAS 2444-36-2] commercially obtainable from e.g. Acros. Carboxylic acid ACI_CC-08: (E)-3-(2-Chlorophenyl)-acrylic acid [CAS 3752-25-8] commercially obtainable from e.g. Acros.

Synthesis of carboxylic acid ACI_CC-09 2-(2-Chlorophenyl)-2-phenyl-acetic acid

Step 1: A solution of 2-chloro benzoyl chloride (1 g, 5.75 mmol) in benzene (10 ml) was added to a suspension of AlCl₃ (842 mg, 6.33 mmol) in benzene (20 ml) at 20° C. and the mixture was heated under reflux for 20 h. The reaction mixture was cooled to room temperature, adjusted to pH ˜3-4 with 1 N hydrochloric acid and finally extracted with ethyl acetate (2×50 ml).

The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography.

Yield: 79% (1 g)

Step 2: 1 M NaHMDS (13.8 ml, 13.8 mmol) was added to a suspension of methoxy methyl triphenylphosphonium chloride (3 g, 13.8 mmol) in dioxane (15 ml) and the mixture was stirred at this temperature for 30 min. A solution of the product just prepared in step 1 (81 g, 4.6 mmol) in THF (10 ml) was then added dropwise and the reaction mixture was heated under reflux for 2 h. The reaction mixture was cooled to room temperature, water was added and the mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification.

Yield: 53% (600 mg) crude

Step 3: 8 N HCl (5 ml) was added to a solution of the product just obtained in step 2 (250 mg, 1.02 mmol) in acetone (5 ml) and the mixture was stirred at 50° C. for 2 h. The reaction mixture was concentrated and the residue was adjusted to a pH of ˜10 with NaHCO₃ solution. The aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification.

Yield: 27% (150 mg)

Step 4: 2-Methyl-2-butene (164 mg, 2.34 mmol) and sodium hydrogen ortho phosphate (407 mg, 2.60 mmol) were added to a solution of the products just obtained in step 3 (150 mg, 0.652 mmol) in THF/tert-butanol/water (ratio=3:3:1; 10 ml) and the reaction mixture was stirred at 20° C. for 16 h. The water was removed from the reaction mixture and the residue was diluted with ethyl acetate. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification.

Yield: 62% (100 mg)

Sulfonyl chloride SCI_CC-01: 2-Chloro-benzenesulfonyl chloride [CAS 2905-23-9] commercially obtainable from e.g. Acros. Sulfonyl chloride SCI_CC-02: 4-Methoxy-2,6-dimethyl-benzenesulfonyl chloride [CAS-] commercially obtainable from e.g. Apolloscientific. Isocyanate ICN_CC-01: 1,2-Dichloro-4-isocyanato-benzene [CAS 102-36-3] commercially obtainable from e.g. Acros. Isocyanate ICN_CC-02: 1-Chloro-2-(isocyanato-methyl)-benzene [CAS 55204-93-8] commercially obtainable from e.g. Acros.

All acid chlorides (ACL_CC-01 to ACL_CC-45), sulfonyl chlorides (SCI_CC-01 to SCI_CC-28), isocyanates (ICN_CC-01 to ICN_CC-14) and aldehydes (ALD_CC-01 to ALD_CC-35) depicted above were commercially available at the time of synthesis.

4) Parallel Synthesis of Dihydroindenes—Library No. 1: General:

The amine units AMN_CC′ were prepared from the Boc-protected amines AMN_CC by Parallel Method 1 or Parallel Method 5 in accordance with the above equation. The amine acid salts AMN_CC′ obtained in this way were reacted in parallel synthesis by Parallel Method 2 with the acids ACI_CC to give the amidic products IND_CC. AMN_CC′ were reacted in parallel synthesis by Parallel Method 3 or Parallel Method 6 with the sulfonyl chlorides SCI_CC to give the sulfonylated products IND_CC. AMN_CC′ were reacted in parallel synthesis by Parallel Method 4 with the isocyanates ICN_CC to give the ureas IND_CC. AMN_CC′ were reacted in parallel synthesis by Parallel Method 7 with the acid chlorides ACL_CC to give amidic products IND_CC. The correlation of products (IND_CC) to the units used (ACI_CC, SCI_CC, ICN_CC and AMN) and can be seen from the synthesis matrix.

The crude products of the parallel synthesis were purified by column chromatography. It was possible to demonstrate the identity of the products by analytical HPLC-MS measurements (cf. HPLC-MS data).

Parallel Method 1: Boc Deprotection

20% trifluoroacetic acid in methylene chloride (10 ml/mol) was added to the corresponding Boc-protected amine (1 eq., AMN_CC) at 0° C. The reaction mixture obtained was stirred at 25° C. for 4 h. The course of the reaction was monitored by means of thin layer chromatography. The solvent was then removed under reduced pressure and the residue was dried thoroughly in order to remove traces of trifluoroacetic acid. The crude product obtained in this way was used for synthesis of the libraries without further purification.

Parallel Method 2: Amide Formation

HATU (2 eq.) was added to a methylene chloride solution (3 ml/mmol) of the acid unit ACI_CC (1 eq.) at 0° C. and the mixture was stirred for 15 min. In a further round-bottomed flask, a methylene chloride solution (1 ml/mmol) of the Boc-deprotected amine unit AMN_CC′ (1.5 eq.) was cooled in an ice bath, DIPEA (3 eq.) was added and the mixture was then added to the acid unit at 0° C. The reaction mixture was stirred at room temperature for 16 h and finally diluted with methylene chloride. The organic phase was washed successively with aqueous NH₄Cl solution, NaHCO₃ solution and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified via a Biotage parallel purification system. Some compounds were purified manually by column chromatography over neutral aluminium oxide with methanol/methylene chloride as the mobile phase. A few compounds were purified via prep. HPLC with an aqueous ammonia method.

Parallel Method 3: Sulfonylation

Diisopropylethylamine (3 eq.) was added dropwise to a suspension of AMN_CC′ (1 eq.) in methylene chloride (4 ml/mmol) at 0° C. and the mixture was stirred further for 15 minutes. The sulfonyl chloride (SCI_CC) (1.1 eq.) was then added at 0° C. and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with methylene chloride and the organic phase was washed successively with water, aqueous NH₄Cl solution and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified via a Biotage parallel purification system. Some compounds were purified manually by column chromatography over neutral aluminium oxide with methanol/methylene chloride as the mobile phase. A few compounds were purified via prep. HPLC with an aqueous ammonia method.

Parallel Method 4: Urea Formation

Diisopropylethylamine (3 eq.) was added dropwise to a suspension of AMN_CC′ (1 eq.) in methylene chloride (4 ml/mmol) at 0° C. and the mixture was stirred further for 15 minutes. The isocyanate (ICN_CC) (1.1 eq.) was then added at 0° C. and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with methylene chloride and the organic phase was washed successively with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified via a Biotage parallel purification system. Some compounds were purified manually by column chromatography over neutral aluminium oxide with methanol/methylene chloride as the mobile phase. A few compounds were purified via prep. HPLC with an aqueous ammonia method.

Parallel Method 5: Boc Deprotection

Acetyl chloride (500 μmol, 35.32 μl) was added at room temperature to the Boc-protected amine AMN_CC (100 μmol) dissolved in 1 ml ethanol. The reaction mixture was stirred at room temperature overnight and the solvent removed under reduced pressure. The crude product AMN_CC′ obtained in this way was used for library synthesis without further purification.

Parallel Method 6: Sulfonylation

Diisopropylethylamine (500 μmol, 85 μl) was added to a suspension of AMN_CC′ (100 μmol) in methylene chloride (1 ml) at room temperature. The sulfonyl chloride (SCI_CC) (150 μmol), dissolved in methylene chloride (1 ml), was then added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was treated with sat. NaCl solution (1 ml) and aqueous NaOH solution (1 mol/L) and stirred at room temperature for 30 minutes. The organic layer was separated and the aqueous phase was extracted with methylene chloride for 2 times. The combined organic phases were concentrated under reduced pressure. The crude product was purified via a HPLC-MS system.

Parallel Method 7: Amide Formation

Diisopropylethylamine (500 μmol, 85 μl) was added to a suspension of AMN_CC′ (100 μmol) in methylene chloride (1 ml) at room temperature. The sulfonyl chloride (ACL_CC) (150 μmol), dissolved in methylene chloride (1 ml), was then added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was treated with sat. NaCl solution (1 ml) and aqueous NaOH solution (1 mol/L) and stirred at room temperature for 30 minutes. The organic layer was separated and the aqueous phase was extracted with methylene chloride for 2 times. The combined organic phases were concentrated under reduced pressure. The crude product was purified via a HPLC-MS system.

Synthesis Matrix:

ACI_CC, SCI_CC or Example no. ICN_CC Amine (AMN_CC) Method no. Ind_CC-001 SCI_CC-02 AMN_CC-01 No. 1 & No. 3 Ind_CC-002 ACI_CC-01 AMN_CC-01 No. 1 & No. 2 Ind_CC-003 ACI_CC-02 AMN_CC-01 No. 1 & No. 2 Ind_CC-004 ACI_CC-03 AMN_CC-01 No. 1 & No. 2 Ind_CC-005 ACI_CC-04 AMN_CC-01 No. 1 & No. 2 Ind_CC-006 ACI_CC-05 AMN_CC-01 No. 1 & No. 2 Ind_CC-007 ACI_CC-07 AMN_CC-01 No. 1 & No. 2 Ind_CC-008 ACI_CC-08 AMN_CC-01 No. 1 & No. 2 Ind_CC-009 ACI_CC-09 AMN_CC-01 No. 1 & No. 2 Ind_CC-010 SCI_CC-01 AMN_CC-01 No. 1 & No. 3 Ind_CC-011 ICN_CC-01 AMN_CC-01 No. 1 & No. 4 Ind_CC-012 ICN_CC-02 AMN_CC-01 No. 1 & No. 4 Ind_CC-013 ACI_CC-06 AMN_CC-01 No. 1 & No. 2 Ind_CC-014 ACI_CC-01 AMN_CC-02 No. 1 & No. 2 Ind_CC-015 ACI_CC-02 AMN_CC-02 No. 1 & No. 2 Ind_CC-016 ACI_CC-03 AMN_CC-02 No. 1 & No. 2 Ind_CC-017 ACI_CC-04 AMN_CC-02 No. 1 & No. 2 Ind_CC-018 ACI_CC-05 AMN_CC-02 No. 1 & No. 2 Ind_CC-019 ACI_CC-07 AMN_CC-02 No. 1 & No. 2 Ind_CC-020 ACI_CC-08 AMN_CC-02 No. 1 & No. 2 Ind_CC-021 ACI_CC-09 AMN_CC-02 No. 1 & No. 2 Ind_CC-022 ICN_CC-01 AMN_CC-02 No. 1 & No. 4 Ind_CC-023 ICN_CC-02 AMN_CC-02 No. 1 & No. 4 Ind_CC-024 SCI_CC-01 AMN_CC-02 No. 1 & No. 3 Ind_CC-025 SCI_CC-02 AMN_CC-02 No. 1 & No. 3 Ind_CC-026 ACI_CC-06 AMN_CC-02 No. 1 & No. 2 Ind_CC-027 ACI_CC-01 AMN_CC-03 No. 1 & No. 2 Ind_CC-028 ACI_CC-02 AMN_CC-03 No. 1 & No. 2 Ind_CC-029 ACI_CC-03 AMN_CC-03 No. 1 & No. 2 Ind_CC-030 ACI_CC-04 AMN_CC-03 No. 1 & No. 2 Ind_CC-031 ACI_CC-05 AMN_CC-03 No. 1 & No. 2 Ind_CC-032 ACI_CC-07 AMN_CC-03 No. 1 & No. 2 Ind_CC-033 ACI_CC-08 AMN_CC-03 No. 1 & No. 2 Ind_CC-034 SCI_CC-01 AMN_CC-03 No. 1 & No. 3 Ind_CC-035 SCI_CC-02 AMN_CC-03 No. 1 & No. 3 Ind_CC-036 ICN_CC-01 AMN_CC-03 No. 1 & No. 4 Ind_CC-037 ICN_CC-02 AMN_CC-03 No. 1 & No. 4 Ind_CC-038 ACI_CC-09 AMN_CC-03 No. 1 & No. 2 Ind_CC-039 ACI_CC-06 AMN_CC-03 No. 1 & No. 2 Ind_CC-040 ACI_CC-01 AMN_CC-04 No. 1 & No. 2 Ind_CC-041 ACI_CC-02 AMN_CC-04 No. 1 & No. 2 Ind_CC-042 ACI_CC-03 AMN_CC-04 No. 1 & No. 2 Ind_CC-043 ACI_CC-04 AMN_CC-04 No. 1 & No. 2 Ind_CC-044 ACI_CC-05 AMN_CC-04 No. 1 & No. 2 Ind_CC-045 ACI_CC-07 AMN_CC-04 No. 1 & No. 2 Ind_CC-046 ACI_CC-08 AMN_CC-04 No. 1 & No. 2 Ind_CC-047 ICN_CC-01 AMN_CC-04 No. 1 & No. 4 Ind_CC-048 ICN_CC-02 AMN_CC-04 No. 1 & No. 4 Ind_CC-049 SCI_CC-01 AMN_CC-04 No. 1 & No. 3 Ind_CC-050 SCI_CC-02 AMN_CC-04 No. 1 & No. 3 Ind_CC-051 ACI_CC-09 AMN_CC-04 No. 1 & No. 2 Ind_CC-052 ACI_CC-01 AMN_CC-13 No. 1 & No. 2 Ind_CC-053 ACI_CC-07 AMN_CC-13 No. 1 & No. 2 Ind_CC-054 ACI_CC-04 AMN_CC-13 No. 1 & No. 2 Ind_CC-055 ACI_CC-03 AMN_CC-13 No. 1 & No. 2 Ind_CC-056 ACI_CC-09 AMN_CC-13 No. 1 & No. 2 Ind_CC-057 ICN_CC-01 AMN_CC-13 No. 1 & No. 4 Ind_CC-058 ACI_CC-02 AMN_CC-13 No. 1 & No. 2 Ind_CC-059 ACI_CC-05 AMN_CC-13 No. 1 & No. 2 Ind_CC-060 ACI_CC-08 AMN_CC-13 No. 1 & No. 2 Ind_CC-061 ICN_CC-02 AMN_CC-13 No. 1 & No. 4 Ind_CC-062 SCI_CC-01 AMN_CC-13 No. 1 & No. 3 Ind_CC-063 SCI_CC-02 AMN_CC-13 No. 1 & No. 3 Ind_CC-064 ACI_CC-02 AMN_CC-14 No. 1 & No. 2 Ind_CC-065 ACI_CC-03 AMN_CC-14 No. 1 & No. 2 Ind_CC-066 ACI_CC-04 AMN_CC-14 No. 1 & No. 2 Ind_CC-067 ACI_CC-05 AMN_CC-14 No. 1 & No. 2 Ind_CC-068 ACI_CC-06 AMN_CC-14 No. 1 & No. 2 Ind_CC-069 ACI_CC-07 AMN_CC-14 No. 1 & No. 2 Ind_CC-070 ACI_CC-08 AMN_CC-14 No. 1 & No. 2 Ind_CC-071 ICN_CC-01 AMN_CC-14 No. 1 & No. 4 Ind_CC-072 SCI_CC-01 AMN_CC-14 No. 1 & No. 3 Ind_CC-073 ICN_CC-02 AMN_CC-14 No. 1 & No. 4 Ind_CC-074 ACI_CC-01 AMN_CC-14 No. 1 & No. 2 Ind_CC-075 ACI_CC-09 AMN_CC-14 No. 1 & No. 2 Ind_CC-076 SCI_CC-02 AMN_CC-14 No. 1 & No. 3 Ind_CC-077 ACI_CC-07 AMN_CC-15 No. 1 & No. 2 Ind_CC-078 ACI_CC-05 AMN_CC-15 No. 1 & No. 2 Ind_CC-079 ACI_CC-04 AMN_CC-15 No. 1 & No. 2 Ind_CC-080 ACI_CC-03 AMN_CC-15 No. 1 & No. 2 Ind_CC-081 ACI_CC-02 AMN_CC-15 No. 1 & No. 2 Ind_CC-082 ACI_CC-09 AMN_CC-15 No. 1 & No. 2 Ind_CC-083 ACI_CC-08 AMN_CC-15 No. 1 & No. 2 Ind_CC-084 ACI_CC-01 AMN_CC-15 No. 1 & No. 2 Ind_CC-085 ICN_CC-01 AMN_CC-15 No. 1 & No. 4 Ind_CC-086 ICN_CC-02 AMN_CC-15 No. 1 & No. 4 Ind_CC-087 SCI_CC-02 AMN_CC-15 No. 1 & No. 3 Ind_CC-088 ACI_CC-06 AMN_CC-15 No. 1 & No. 2 Ind_CC-089 SCI_CC-01 AMN_CC-15 No. 1 & No. 3 IND_CC-200 ACL_CC-42 AMN_CC-02 No. 5 & No. 7 IND_CC-201 ACL_CC-40 AMN_CC-02 No. 5 & No. 7 IND_CC-202 ACL_CC-36 AMN_CC-02 No. 5 & No. 7 IND_CC-203 ACL_CC-35 AMN_CC-02 No. 5 & No. 7 IND_CC-204 ACL_CC-43 AMN_CC-01 No. 5 & No. 7 IND_CC-205 ACL_CC-43 AMN_CC-04 No. 5 & No. 7 IND_CC-206 ACL_CC-43 AMN_CC-14 No. 5 & No. 7 IND_CC-207 ACL_CC-42 AMN_CC-01 No. 5 & No. 7 IND_CC-208 ACL_CC-42 AMN_CC-04 No. 5 & No. 7 IND_CC-209 ACL_CC-42 AMN_CC-03 No. 5 & No. 7 IND_CC-210 ACL_CC-42 AMN_CC-14 No. 5 & No. 7 IND_CC-211 ACL_CC-40 AMN_CC-01 No. 5 & No. 7 IND_CC-212 ACL_CC-40 AMN_CC-04 No. 5 & No. 7 IND_CC-213 ACL_CC-40 AMN_CC-03 No. 5 & No. 7 IND_CC-214 ACL_CC-39 AMN_CC-01 No. 5 & No. 7 IND_CC-215 ACL_CC-39 AMN_CC-04 No. 5 & No. 7 IND_CC-216 ACL_CC-39 AMN_CC-14 No. 5 & No. 7 IND_CC-217 ACL_CC-36 AMN_CC-01 No. 5 & No. 7 IND_CC-218 ACL_CC-36 AMN_CC-04 No. 5 & No. 7 IND_CC-219 ACL_CC-36 AMN_CC-14 No. 5 & No. 7 IND_CC-220 ACL_CC-35 AMN_CC-01 No. 5 & No. 7 IND_CC-221 ACL_CC-35 AMN_CC-04 No. 5 & No. 7 IND_CC-222 ACL_CC-35 AMN_CC-03 No. 5 & No. 7 IND_CC-223 ACL_CC-35 AMN_CC-14 No. 5 & No. 7 IND_CC-224 ACL_CC-34 AMN_CC-02 No. 5 & No. 7 IND_CC-225 ACL_CC-32 AMN_CC-02 No. 5 & No. 7 IND_CC-226 SCI_CC-27 AMN_CC-02 No. 5 & No. 6 IND_CC-227 SCI_CC-26 AMN_CC-02 No. 5 & No. 6 IND_CC-228 ACL_CC-34 AMN_CC-01 No. 5 & No. 7 IND_CC-229 ACL_CC-34 AMN_CC-04 No. 5 & No. 7 IND_CC-230 ACL_CC-34 AMN_CC-03 No. 5 & No. 7 IND_CC-231 ACL_CC-34 AMN_CC-14 No. 5 & No. 7 IND_CC-232 ACL_CC-32 AMN_CC-01 No. 5 & No. 7 IND_CC-233 ACL_CC-32 AMN_CC-04 No. 5 & No. 7 IND_CC-234 ACL_CC-32 AMN_CC-14 No. 5 & No. 7 IND_CC-235 ACL_CC-31 AMN_CC-03 No. 5 & No. 7 IND_CC-236 SCI_CC-27 AMN_CC-01 No. 5 & No. 6 IND_CC-237 SCI_CC-27 AMN_CC-04 No. 5 & No. 6 IND_CC-238 SCI_CC-27 AMN_CC-14 No. 5 & No. 6 IND_CC-239 SCI_CC-26 AMN_CC-03 No. 5 & No. 6 IND_CC-240 SCI_CC-26 AMN_CC-14 No. 5 & No. 6 IND_CC-241 SCI_CC-21 AMN_CC-01 No. 5 & No. 6 IND_CC-242 SCI_CC-21 AMN_CC-14 No. 5 & No. 6 IND_CC-243 ACL_CC-43 AMN_CC-13 No. 5 & No. 7 IND_CC-244 ACL_CC-42 AMN_CC-13 No. 5 & No. 7 IND_CC-245 ACL_CC-42 AMN_CC-15 No. 5 & No. 7 IND_CC-246 ACL_CC-40 AMN_CC-13 No. 5 & No. 7 IND_CC-247 ACL_CC-40 AMN_CC-15 No. 5 & No. 7 IND_CC-248 ACL_CC-39 AMN_CC-13 No. 5 & No. 7 IND_CC-249 ACL_CC-39 AMN_CC-15 No. 5 & No. 7 IND_CC-250 ACL_CC-36 AMN_CC-13 No. 5 & No. 7 IND_CC-251 ACL_CC-36 AMN_CC-15 No. 5 & No. 7 IND_CC-252 ACL_CC-35 AMN_CC-13 No. 5 & No. 7 IND_CC-253 ACL_CC-35 AMN_CC-15 No. 5 & No. 7 IND_CC-254 ACL_CC-32 AMN_CC-13 No. 5 & No. 7 IND_CC-255 ACL_CC-32 AMN_CC-15 No. 5 & No. 7 IND_CC-256 SCI_CC-27 AMN_CC-13 No. 5 & No. 6 IND_CC-258 SCI_CC-27 AMN_CC-15 No. 5 & No. 6 IND_CC-259 SCI_CC-26 AMN_CC-13 No. 5 & No. 6 IND_CC-260 SCI_CC-21 AMN_CC-13 No. 5 & No. 6 IND_CC-261 ACL_CC-28 AMN_CC-02 No. 5 & No. 7 IND_CC-262 ACL_CC-28 AMN_CC-01 No. 5 & No. 7 IND_CC-263 ACL_CC-28 AMN_CC-04 No. 5 & No. 7 IND_CC-264 ACL_CC-27 AMN_CC-04 No. 5 & No. 7 IND_CC-265 ACL_CC-26 AMN_CC-02 No. 5 & No. 7 IND_CC-266 ACL_CC-26 AMN_CC-01 No. 5 & No. 7 IND_CC-267 ACL_CC-26 AMN_CC-04 No. 5 & No. 7 IND_CC-268 ACL_CC-03 AMN_CC-02 No. 5 & No. 7 IND_CC-269 ACL_CC-03 AMN_CC-01 No. 5 & No. 7 IND_CC-270 ACL_CC-03 AMN_CC-04 No. 5 & No. 7 IND_CC-271 ACL_CC-01 AMN_CC-04 No. 5 & No. 7 IND_CC-272 ACL_CC-01 AMN_CC-02 No. 5 & No. 7 IND_CC-273 ACL_CC-01 AMN_CC-01 No. 5 & No. 7 IND_CC-274 ACL_CC-28 AMN_CC-03 No. 5 & No. 7 IND_CC-275 ACL_CC-28 AMN_CC-14 No. 5 & No. 7 IND_CC-276 ACL_CC-28 AMN_CC-13 No. 5 & No. 7 IND_CC-277 ACL_CC-28 AMN_CC-15 No. 5 & No. 7 IND_CC-278 ACL_CC-27 AMN_CC-03 No. 5 & No. 7 IND_CC-279 ACL_CC-27 AMN_CC-13 No. 5 & No. 7 IND_CC-280 ACL_CC-27 AMN_CC-15 No. 5 & No. 7 IND_CC-281 ACL_CC-26 AMN_CC-03 No. 5 & No. 7 IND_CC-282 ACL_CC-26 AMN_CC-14 No. 5 & No. 7 IND_CC-283 ACL_CC-26 AMN_CC-13 No. 5 & No. 7 IND_CC-284 ACL_CC-26 AMN_CC-15 No. 5 & No. 7 IND_CC-286 ACL_CC-03 AMN_CC-03 No. 5 & No. 7 IND_CC-287 ACL_CC-03 AMN_CC-14 No. 5 & No. 7 IND_CC-288 ACL_CC-03 AMN_CC-13 No. 5 & No. 7 IND_CC-289 ACL_CC-03 AMN_CC-15 No. 5 & No. 7 IND_CC-290 ACL_CC-01 AMN_CC-03 No. 5 & No. 7 IND_CC-291 ACL_CC-01 AMN_CC-14 No. 5 & No. 7 IND_CC-292 ACL_CC-01 AMN_CC-13 No. 5 & No. 7 IND_CC-293 ACL_CC-01 AMN_CC-15 No. 5 & No. 7 IND_CC-294 ACL_CC-45 AMN_CC-01 No. 5 & No. 7 IND_CC-295 ACL_CC-45 AMN_CC-04 No. 5 & No. 7 IND_CC-296 ACL_CC-44 AMN_CC-02 No. 5 & No. 7 IND_CC-297 ACL_CC-44 AMN_CC-01 No. 5 & No. 7 IND_CC-298 ACL_CC-44 AMN_CC-04 No. 5 & No. 7 IND_CC-299 ACL_CC-41 AMN_CC-02 No. 5 & No. 7 IND_CC-300 ACL_CC-41 AMN_CC-01 No. 5 & No. 7 IND_CC-301 ACL_CC-37 AMN_CC-02 No. 5 & No. 7 IND_CC-302 ACL_CC-37 AMN_CC-01 No. 5 & No. 7 IND_CC-303 ACL_CC-37 AMN_CC-04 No. 5 & No. 7 IND_CC-304 ACL_CC-33 AMN_CC-02 No. 5 & No. 7 IND_CC-305 ACL_CC-33 AMN_CC-01 No. 5 & No. 7 IND_CC-306 ACL_CC-33 AMN_CC-04 No. 5 & No. 7 IND_CC-307 ACL_CC-45 AMN_CC-03 No. 5 & No. 7 IND_CC-308 ACL_CC-45 AMN_CC-14 No. 5 & No. 7 IND_CC-309 ACL_CC-45 AMN_CC-13 No. 5 & No. 7 IND_CC-310 ACL_CC-45 AMN_CC-15 No. 5 & No. 7 IND_CC-311 ACL_CC-44 AMN_CC-14 No. 5 & No. 7 IND_CC-312 ACL_CC-44 AMN_CC-13 No. 5 & No. 7 IND_CC-313 ACL_CC-44 AMN_CC-15 No. 5 & No. 7 IND_CC-314 ACL_CC-37 AMN_CC-14 No. 5 & No. 7 IND_CC-315 ACL_CC-37 AMN_CC-13 No. 5 & No. 7 IND_CC-316 ACL_CC-37 AMN_CC-15 No. 5 & No. 7 IND_CC-317 ACL_CC-33 AMN_CC-14 No. 5 & No. 7 IND_CC-318 ACL_CC-33 AMN_CC-13 No. 5 & No. 7 IND_CC-319 ACL_CC-33 AMN_CC-15 No. 5 & No. 7 IND_CC-320 SCI_CC-24 AMN_CC-02 No. 5 & No. 6 IND_CC-321 SCI_CC-12 AMN_CC-02 No. 5 & No. 6 IND_CC-322 SCI_CC-12 AMN_CC-01 No. 5 & No. 6 IND_CC-323 SCI_CC-12 AMN_CC-04 No. 5 & No. 6 IND_CC-324 SCI_CC-11 AMN_CC-02 No. 5 & No. 6 IND_CC-325 SCI_CC-06 AMN_CC-02 No. 5 & No. 6 IND_CC-326 SCI_CC-05 AMN_CC-02 No. 5 & No. 6 IND_CC-327 SCI_CC-09 AMN_CC-02 No. 5 & No. 6 IND_CC-328 SCI_CC-09 AMN_CC-01 No. 5 & No. 6 IND_CC-329 SCI_CC-09 AMN_CC-04 No. 5 & No. 6 IND_CC-330 SCI_CC-24 AMN_CC-14 No. 5 & No. 6 IND_CC-331 SCI_CC-24 AMN_CC-13 No. 5 & No. 6 IND_CC-332 SCI_CC-12 AMN_CC-13 No. 5 & No. 6 IND_CC-333 SCI_CC-12 AMN_CC-15 No. 5 & No. 6 IND_CC-334 SCI_CC-11 AMN_CC-14 No. 5 & No. 6 IND_CC-335 SCI_CC-11 AMN_CC-13 No. 5 & No. 6 IND_CC-336 SCI_CC-06 AMN_CC-14 No. 5 & No. 6 IND_CC-337 SCI_CC-06 AMN_CC-13 No. 5 & No. 6 IND_CC-338 SCI_CC-05 AMN_CC-14 No. 5 & No. 6 IND_CC-339 SCI_CC-05 AMN_CC-13 No. 5 & No. 6 IND_CC-340 SCI_CC-09 AMN_CC-13 No. 5 & No. 6 IND_CC-341 SCI_CC-09 AMN_CC-14 No. 5 & No. 6 IND_CC-342 SCI_CC-09 AMN_CC-15 No. 5 & No. 6 IND_CC-343 SCI_CC-13 AMN_CC-02 No. 5 & No. 6 IND_CC-344 SCI_CC-10 AMN_CC-02 No. 5 & No. 6 IND_CC-345 ACL_CC-04 AMN_CC-02 No. 5 & No. 7 IND_CC-346 ACL_CC-04 AMN_CC-01 No. 5 & No. 7 IND_CC-347 ACL_CC-04 AMN_CC-04 No. 5 & No. 7 IND_CC-348 SCI_CC-19 AMN_CC-02 No. 5 & No. 6 IND_CC-349 SCI_CC-19 AMN_CC-01 No. 5 & No. 6 IND_CC-350 SCI_CC-19 AMN_CC-04 No. 5 & No. 6 IND_CC-351 SCI_CC-20 AMN_CC-02 No. 5 & No. 6 IND_CC-352 SCI_CC-20 AMN_CC-01 No. 5 & No. 6 IND_CC-353 SCI_CC-20 AMN_CC-04 No. 5 & No. 6 IND_CC-354 SCI_CC-28 AMN_CC-02 No. 5 & No. 6 IND_CC-355 SCI_CC-28 AMN_CC-01 No. 5 & No. 6 IND_CC-356 SCI_CC-28 AMN_CC-04 No. 5 & No. 6 IND_CC-357 SCI_CC-10 AMN_CC-15 No. 5 & No. 6 IND_CC-358 ACL_CC-04 AMN_CC-15 No. 5 & No. 7 IND_CC-359 SCI_CC-19 AMN_CC-15 No. 5 & No. 6 IND_CC-360 SCI_CC-20 AMN_CC-15 No. 5 & No. 6 IND_CC-361 SCI_CC-28 AMN_CC-15 No. 5 & No. 6 IND_CC-362 SCI_CC-17 AMN_CC-02 No. 5 & No. 6 IND_CC-363 SCI_CC-17 AMN_CC-04 No. 5 & No. 6 IND_CC-364 ACL_CC-09 AMN_CC-01 No. 5 & No. 7 IND_CC-365 ACL_CC-09 AMN_CC-02 No. 5 & No. 7 IND_CC-366 ACL_CC-09 AMN_CC-04 No. 5 & No. 7 IND_CC-367 ACL_CC-09 AMN_CC-15 No. 5 & No. 7 IND_CC-368 ACL_CC-15 AMN_CC-01 No. 5 & No. 7 IND_CC-369 ACL_CC-15 AMN_CC-02 No. 5 & No. 7 IND_CC-370 ACL_CC-15 AMN_CC-15 No. 5 & No. 7 IND_CC-371 ACL_CC-18 AMN_CC-01 No. 5 & No. 7 IND_CC-372 ACL_CC-18 AMN_CC-02 No. 5 & No. 7 IND_CC-373 ACL_CC-18 AMN_CC-04 No. 5 & No. 7 IND_CC-374 ACL_CC-18 AMN_CC-15 No. 5 & No. 7 IND_CC-375 ACL_CC-29 AMN_CC-15 No. 5 & No. 7 IND_CC-376 ACL_CC-06 AMN_CC-01 No. 5 & No. 7 IND_CC-377 ACL_CC-06 AMN_CC-04 No. 5 & No. 7 IND_CC-378 ACL_CC-06 AMN_CC-15 No. 5 & No. 7 IND_CC-379 ACL_CC-08 AMN_CC-01 No. 5 & No. 7 IND_CC-380 ACL_CC-08 AMN_CC-02 No. 5 & No. 7 IND_CC-381 ACL_CC-08 AMN_CC-04 No. 5 & No. 7 IND_CC-382 ACL_CC-08 AMN_CC-15 No. 5 & No. 7 IND_CC-383 ACL_CC-17 AMN_CC-01 No. 5 & No. 7 IND_CC-384 ACL_CC-17 AMN_CC-02 No. 5 & No. 7 IND_CC-385 ACL_CC-17 AMN_CC-04 No. 5 & No. 7 IND_CC-386 ACL_CC-17 AMN_CC-15 No. 5 & No. 7 IND_CC-387 ACL_CC-25 AMN_CC-02 No. 5 & No. 7 IND_CC-388 ACL_CC-25 AMN_CC-04 No. 5 & No. 7 IND_CC-389 ACL_CC-25 AMN_CC-15 No. 5 & No. 7 IND_CC-390 SCI_CC-18 AMN_CC-02 No. 5 & No. 6 IND_CC-391 ACL_CC-13 AMN_CC-01 No. 5 & No. 7 IND_CC-392 ACL_CC-13 AMN_CC-02 No. 5 & No. 7 IND_CC-393 ACL_CC-13 AMN_CC-04 No. 5 & No. 7 IND_CC-394 ACL_CC-13 AMN_CC-15 No. 5 & No. 7 IND_CC-395 ACL_CC-30 AMN_CC-02 No. 5 & No. 7 IND_CC-396 ACL_CC-30 AMN_CC-15 No. 5 & No. 7 IND_CC-397 ACL_CC-38 AMN_CC-01 No. 5 & No. 7 IND_CC-398 ACL_CC-38 AMN_CC-15 No. 5 & No. 7 IND_CC-399 ACL_CC-02 AMN_CC-01 No. 5 & No. 7 IND_CC-400 ACL_CC-02 AMN_CC-02 No. 5 & No. 7 IND_CC-401 ACL_CC-02 AMN_CC-04 No. 5 & No. 7 IND_CC-402 ACL_CC-02 AMN_CC-15 No. 5 & No. 7 IND_CC-403 SCI_CC-25 AMN_CC-02 No. 5 & No. 6 IND_CC-404 SCI_CC-25 AMN_CC-15 No. 5 & No. 6 IND_CC-405 SCI_CC-15 AMN_CC-02 No. 5 & No. 6 IND_CC-406 SCI_CC-14 AMN_CC-02 No. 5 & No. 6 IND_CC-407 SCI_CC-14 AMN_CC-15 No. 5 & No. 6 IND_CC-408 ACL_CC-10 AMN_CC-02 No. 5 & No. 7 IND_CC-409 ACL_CC-10 AMN_CC-15 No. 5 & No. 7 IND_CC-410 ACL_CC-11 AMN_CC-02 No. 5 & No. 7 IND_CC-411 ACL_CC-11 AMN_CC-15 No. 5 & No. 7 IND_CC-412 ACL_CC-12 AMN_CC-02 No. 5 & No. 7 IND_CC-413 ACL_CC-12 AMN_CC-15 No. 5 & No. 7 IND_CC-414 ACL_CC-14 AMN_CC-02 No. 5 & No. 7 IND_CC-415 ACL_CC-14 AMN_CC-15 No. 5 & No. 7 IND_CC-416 ACL_CC-16 AMN_CC-02 No. 5 & No. 7 IND_CC-417 ACL_CC-16 AMN_CC-15 No. 5 & No. 7 IND_CC-418 ACL_CC-19 AMN_CC-02 No. 5 & No. 7 IND_CC-419 ACL_CC-19 AMN_CC-15 No. 5 & No. 7 IND_CC-420 ACL_CC-23 AMN_CC-15 No. 5 & No. 7

Analytical Data:

Example no. [M+] found R.t. [min] Ind_CC-001 589.4 2.83 Ind_CC-002 496 2.65 Ind_CC-003 563 2.76 Ind_CC-004 535 2.77 Ind_CC-005 535 2.81 Ind_CC-006 563 2.8 Ind_CC-007 543.2 2.74 Ind_CC-008 555.2 2.84 Ind_CC-009 619.3 2.92 Ind_CC-010 565.4 2.78 Ind_CC-011 578.2 2.89 Ind_CC-012 558.4 2.75 Ind_CC-013 553.2 2.73 Ind_CC-014 510.2 2.52 Ind_CC-015 577.2 2.79 Ind_CC-016 549.4 2.76 Ind_CC-017 549.2 2.83 Ind_CC-018 577.2 2.85 Ind_CC-019 557.2 2.8 Ind_CC-020 569.2 2.86 Ind_CC-021 633.3 2.98 Ind_CC-022 592.2 2.93 Ind_CC-023 572.2 2.8 Ind_CC-024 579.2 2.86 Ind_CC-025 603.4 2.91 Ind_CC-027 563.2 3.93 Ind_CC-028 630.3 3.94 Ind_CC-029 602.1 4.07 Ind_CC-030 602.3 4.13 Ind_CC-031 630.3 4.07 Ind_CC-032 610.4 3.98 Ind_CC-033 622.3 4.08 Ind_CC-034 632.2 4.05 Ind_CC-035 656.3 4.14 Ind_CC-036 645.3 4.28 Ind_CC-037 625.2 3.92 Ind_CC-038 686.3 4.2 Ind_CC-040 482.2 2.62 Ind_CC-041 549.4 2.71 Ind_CC-042 521.2 2.74 Ind_CC-043 521.2 2.78 Ind_CC-044 549.4 2.78 Ind_CC-045 529.2 2.71 Ind_CC-046 541.4 2.81 Ind_CC-047 564.2 2.89 Ind_CC-048 544.2 2.74 Ind_CC-049 551.2 2.77 Ind_CC-050 575.2 2.82 Ind_CC-051 605.4 2.9 Ind_CC-052 524.4 2.78 Ind_CC-053 571.2 2.84 Ind_CC-054 563 2.9 Ind_CC-055 563 2.87 Ind_CC-056 647.4 3 Ind_CC-057 606.4 2.99 Ind_CC-058 591.2 6.73 Ind_CC-059 591.2 2.89 Ind_CC-060 583.2 2.92 Ind_CC-061 586.2 2.84 Ind_CC-062 593.4 2.89 Ind_CC-064 591.2 2.9 Ind_CC-065 563 2.93 Ind_CC-066 563.2 2.97 Ind_CC-067 591.4 2.94 Ind_CC-068 581.6 2.85 Ind_CC-069 571.2 2.89 Ind_CC-070 583.4 2.98 Ind_CC-071 606.3 3.06 Ind_CC-072 593.2 2.93 Ind_CC-073 586.4 2.87 Ind_CC-074 524.4 2.79 Ind_CC-075 647.4 3.01 Ind_CC-076 617.4 2.92 Ind_CC-077 529.2 2.69 Ind_CC-078 549.4 2.74 Ind_CC-079 521.2 2.74 Ind_CC-080 521.2 2.7 Ind_CC-081 549.2 2.69 Ind_CC-082 605.4 2.88 Ind_CC-083 541.4 2.77 Ind_CC-084 482 2.55 Ind_CC-085 564.2 2.86 Ind_CC-086 544.4 2.71 IND_CC-200 577.3 0.57 IND_CC-201 573.4 0.55 IND_CC-202 611.4 0.58 IND_CC-203 561.3 0.54 IND_CC-204 597.3 0.54 IND_CC-205 538.3 0.53 IND_CC-206 625.4 0.58 IND_CC-207 563.3 0.53 IND_CC-208 549.3 0.52 IND_CC-209 630.3 0.89 IND_CC-210 591.3 0.57 IND_CC-211 559.3 0.52 IND_CC-212 545.3 0.51 IND_CC-213 626.4 0.86 IND_CC-214 561.3 0.53 IND_CC-215 547.3 0.52 IND_CC-216 589.4 0.57 IND_CC-217 597.3 0.55 IND_CC-218 583.3 0.54 IND_CC-219 625.4 0.59 IND_CC-220 547.3 0.51 IND_CC-221 533.3 0.50 IND_CC-222 614.3 0.86 IND_CC-223 575.4 0.55 IND_CC-224 579.3 0.55 IND_CC-225 611.4 0.56 IND_CC-226 627.4 0.59 IND_CC-227 593.3 0.59 IND_CC-228 565.3 0.52 IND_CC-229 551.3 0.51 IND_CC-230 632.3 0.87 IND_CC-231 593.4 0.58 IND_CC-232 597.4 0.56 IND_CC-233 583.3 0.55 IND_CC-234 525.4 0.60 IND_CC-235 587.4 0.77 IND_CC-236 613.4 0.57 IND_CC-237 599.4 0.57 IND_CC-238 641.4 0.61 IND_CC-239 646.3 0.90 IND_CC-240 607.4 0.61 IND_CC-241 593.4 0.58 IND_CC-242 621.4 0.61 IND_CC-243 625.4 0.59 IND_CC-244 591.4 0.59 IND_CC-245 549.3 0.52 IND_CC-246 587.4 0.57 IND_CC-247 545.3 0.51 IND_CC-248 589.4 0.58 IND_CC-249 547.3 0.51 IND_CC-250 625.4 0.59 IND_CC-251 583.3 0.54 IND_CC-252 575.4 0.56 IND_CC-253 533.3 0.50 IND_CC-254 625.4 0.60 IND_CC-255 583.3 0.54 IND_CC-256 641.4 0.61 IND_CC-258 599.4 0.56 IND_CC-259 607.4 0.60 IND_CC-260 621.4 0.61 IND_CC-261 561.4 0.55 IND_CC-262 547.3 0.52 IND_CC-263 533.3 0.52 IND_CC-264 533.3 0.51 IND_CC-265 577.3 0.57 IND_CC-266 563.3 0.54 IND_CC-267 549.3 0.54 IND_CC-268 577.3 0.56 IND_CC-269 563.3 0.53 IND_CC-270 549.3 0.52 IND_CC-271 515.3 0.50 IND_CC-272 543.3 0.54 IND_CC-273 529.3 0.51 IND_CC-274 614.3 0.86 IND_CC-275 575.4 0.56 IND_CC-276 575.4 0.56 IND_CC-277 533.3 0.50 IND_CC-278 614.3 0.86 IND_CC-279 575.4 0.56 IND_CC-280 533.3 0.49 IND_CC-281 630.2 0.88 IND_CC-282 591.3 0.58 IND_CC-283 591.3 0.58 IND_CC-284 549.3 0.52 IND_CC-286 630.3 0.87 IND_CC-287 591.3 0.57 IND_CC-288 591.3 0.57 IND_CC-289 549.3 0.51 IND_CC-290 596.3 0.85 IND_CC-291 557.3 0.51 IND_CC-292 557.3 0.55 IND_CC-293 515.3 0.49 IND_CC-294 523.4 0.52 IND_CC-295 509.4 0.52 IND_CC-296 557.4 0.54 IND_CC-297 543.4 0.52 IND_CC-298 529.3 0.52 IND_CC-299 607.4 0.59 IND_CC-300 593.4 0.57 IND_CC-301 611.3 0.58 IND_CC-302 597.3 0.56 IND_CC-303 583.3 0.55 IND_CC-304 541.4 0.56 IND_CC-305 527.4 0.54 IND_CC-306 513.3 0.54 IND_CC-307 590.4 0.86 IND_CC-308 551.4 0.57 IND_CC-309 551.4 0.58 IND_CC-310 509.4 0.51 IND_CC-311 571.4 0.57 IND_CC-312 571.4 0.57 IND_CC-313 529.3 0.51 IND_CC-314 625.4 0.61 IND_CC-315 625.4 0.61 IND_CC-316 583.3 0.56 IND_CC-317 555.4 0.59 IND_CC-318 555.4 0.59 IND_CC-319 513.4 0.53 IND_CC-320 647.3 0.63 IND_CC-321 613.3 0.60 IND_CC-322 599.3 0.58 IND_CC-323 585.3 0.57 IND_CC-324 613.3 0.62 IND_CC-325 579.4 0.59 IND_CC-326 577.4 0.60 IND_CC-327 613.4 0.61 IND_CC-328 599.4 0.59 IND_CC-329 585.3 0.58 IND_CC-330 661.4 0.64 IND_CC-331 661.4 0.65 IND_CC-332 627.3 0.62 IND_CC-333 585.2 0.56 IND_CC-334 627.3 0.63 IND_CC-335 627.3 0.64 IND_CC-336 593.4 0.60 IND_CC-337 593.4 0.60 IND_CC-338 591.4 0.61 IND_CC-339 591.4 0.61 IND_CC-340 627.4 0.62 IND_CC-341 627.4 0.62 IND_CC-342 585.3 0.57 IND_CC-343 616.3 0.62 IND_CC-344 613.3 0.62 IND_CC-345 523.4 0.55 IND_CC-346 509.4 0.53 IND_CC-347 495.4 0.52 IND_CC-348 577.4 0.57 IND_CC-349 563.4 0.55 IND_CC-350 549.3 0.54 IND_CC-351 593.4 0.60 IND_CC-352 579.3 0.57 IND_CC-353 565.3 0.57 IND_CC-354 591.4 0.62 IND_CC-355 577.4 0.59 IND_CC-356 563.3 0.58 IND_CC-357 585.3 0.58 IND_CC-358 514.3 0.54 IND_CC-359 549.3 0.53 IND_CC-360 565.3 0.56 IND_CC-361 563.4 0.58 IND_CC-362 647.3 0.65 IND_CC-363 619.2 0.63 IND_CC-364 501.4 0.53 IND_CC-365 515.4 0.56 IND_CC-366 487.4 0.52 IND_CC-367 487.4 0.51 IND_CC-368 459.4 0.46 IND_CC-369 473.4 0.49 IND_CC-370 445.4 0.44 IND_CC-371 489.4 0.51 IND_CC-372 503.4 0.55 IND_CC-373 475.4 0.51 IND_CC-374 475.4 0.49 IND_CC-375 419.3 0.40 IND_CC-376 581.3 0.54 IND_CC-377 567.3 0.53 IND_CC-378 567.3 0.52 IND_CC-379 581.3 0.54 IND_CC-380 595.4 0.57 IND_CC-381 567.3 0.53 IND_CC-382 567.3 0.53 IND_CC-383 531.3 0.51 IND_CC-384 545.3 0.54 IND_CC-385 517.3 0.51 IND_CC-386 517.3 0.49 IND_CC-387 537.4 0.57 IND_CC-388 509.3 0.54 IND_CC-389 509.3 0.52 IND_CC-390 627.3 0.62 IND_CC-391 487.4 0.50 IND_CC-392 501.4 0.54 IND_CC-393 473.4 0.50 IND_CC-394 473.3 0.49 IND_CC-395 578.3 0.55 IND_CC-396 550.3 0.55 IND_CC-397 497.3 0.47 IND_CC-398 483.3 0.46 IND_CC-399 513.3 0.52 IND_CC-400 527.3 0.54 IND_CC-401 499.3 0.51 IND_CC-402 499.3 0.50 IND_CC-403 681.3 0.65 IND_CC-404 653.2 0.61 IND_CC-405 657.2 0.62 IND_CC-406 647.2 0.64 IND_CC-407 619.2 0.60 IND_CC-408 589.4 0.53 IND_CC-409 461.4 0.48 IND_CC-410 475.4 0.51 IND_CC-411 447.3 0.45 IND_CC-412 529.4 0.59 IND_CC-413 501.4 0.54 IND_CC-414 487.4 0.52 IND_CC-415 459.3 0.46 IND_CC-416 489.4 0.53 IND_CC-417 461.3 0.48 IND_CC-418 475.4 0.51 IND_CC-419 447.3 0.45 IND_CC-420 475.4 0.49

E. Parallel Synthesis Library No. 2: 1) Intermediate Syntheses Synthesis of: 3-Amino-2,3-dihydro-1H-indene-5-carboxylic acid tert-butyl ester

Step 1: Triethylamine (10.3 mmol, 3 eq.) and benzyl chloroformate (5.15 mmol, 1.5 eq.) was added to a solution of amine ester A (3.434 mmol) in DMF at 0° C. and the mixture was then stirred at room temperature for 16 h. The mixture was then diluted with ethyl acetate, washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase ethyl acetate/hexane). Yield: 80%

Step 2: The product just obtained in step 1 (0.33 g, 1.015 mmol) was dissolved in 10 ml of a THF-methanol-water mixture (3:1:1), LiOH.H₂O (0.127 g, 3.046 mmol) was added in portions at 0° C. and the mixture was stirred at room temperature for 8 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether and acidified with 10% strength citric acid at 0° C. in order to obtain the desired acid in the form of a white solid. This was filtered out, washed with water and dried at 60° C. for 24 h. Yield: 85%

Step 3: The product just obtained in step 2 (1 g, 3.2 mmol) was dissolved in methylene chloride (20 ml), oxalyl chloride (3.37 ml, 3.53 mmol) and DMF (0.25 ml) were added and the mixture was stirred at room temperature for 2 h. The solvent was removed under reduced pressure and the residue was taken up in chloroform (10 ml) and tert-butanol (9 ml). Pyridine was added at 10° C. and the mixture was stirred for 30 minutes. The reaction mixture was concentrated and the residue was taken up in toluene, and washed with 2 M HCl, sat. NaHCO₃ solution and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate/hexane). Yield: 50%

Step 4: The product just obtained in step 3 (610 mg, 1.66 mmol) was dissolved in methanol (30 ml) and the solution was degassed under argon. Pd(OH)₂ (300 mg) and acetic acid (0.1 ml) were added and the reaction mixture was hydrogenated for 2 h (2 kg of h₂). The reaction mixture was filtered over Celite and the filtrate was concentrated to dryness. The crude product was employed in the next step without further purification.

Yield: 100%

2) Synthesis of the Amine Units (AMN_CC): Overview:

AMN-CC unit no. Structure AMN-CC name AMN_CC-20

9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3- carboxylic acid tert-butyl ester AMN_CC-21

9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3- ^(N)carboxylic acid tert-butyl ester AMN_CC-22

9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane- 3-carboxylic acid tert-butyl ester AMN_CC-23

9-(pyridin-4-yl-methyl)-3,9- diazaspiro[5.5]undecane-3-carboxylic acid tert- butyl ester AMN_CC-24

9-dimethylamino-9-(4-fluorophenyl)-3- azaspiro[5.5]undecane-3-carboxylic acid tert- butyl ester AMN_CC-25

8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2- carboxylic acid tert-butyl ester AMN_CC-26

2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8- carboxylic acid tert-butyl ester

Synthesis of Amine (AMN_CC-20) 9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (AMN_CC-20)

The synthesis of AMN_CC-20 was carried out as described in the context of the synthesis of AMN-01.

Synthesis of Amine (AMN_CC-21) 9-Pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (AMN_CC-21)

BINAP (147 mg, 0.23 mmol) and Pd(OAc)₂ (159 mg, 0.74 mmol) was added to a mixture of 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (3 g, 11.81 mmol), 3-bromopyridine HCl (2.29 g, 11.81 mmol) and sodium tert-butylate (3.4 g, 35.45 mmol) in toluene and the reaction mixture was degassed under argon for 20 minutes and heated under reflux for 4 h. After cooling to room temperature, the mixture was diluted with ethyl acetate, stirred for 15 minutes and filtered over Celite. The reaction mixture was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 31%

Synthesis of Amine (AMN_CC-22) 9-(4-Fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (AMN_CC-22)

BINAP (350 mg, 0.47 mmol) and Pd₂ dba₃ (317 mg, 1.57 mmol) was added to a mixture of 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (2 g, 7.87 mmol), 1-bromo-4-fluoro-benzene (1.3 g, 7.87 mmol) and sodium tert-butylate (2.26 g, 23.61 mmol) in toluene (25 ml) and the reaction mixture was degassed under argon for 20 minutes and heated under reflux for 4 h. The mixture was then diluted with ethyl acetate, stirred for 15 minutes and filtered over Celite. The reaction mixture was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 43%

Synthesis of Amine (AMN_CC-23) 9-(Pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (AMN_CC-23)

NaH (60% strength in mineral oil, 709 mg, 29.52 mmol) was added to a mixture of 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (2.5 g, 9.84 mmol) in DMF (50 ml) at 0° C., the mixture was stirred at room temperature for 2 h, 4-(bromomethyl)-pyridine HCl (2.42 mg, 14.76 mmol) was then added and the mixture was stirred at room temperature for 16 h. Finally, ice was added and the reaction mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase methanol/methylene chloride). Yield: 35%

Synthesis of Amine (AMN_CC-24) 9-Dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (AMN_CC-24)

Step 1: Boc anhydride (190.8 mmol, 1.5 eq.) and triethylamine (254.4 mmol, 2 eq.) was added to a solution of piperidine-4-carboxylic acid methyl ester (127.2 mmol, 1 eq.) in methylene chloride (200 ml) and the mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with methylene chloride (100 ml) and washed with dist. water and sat. NaCl solution and the organic phase was dried over sodium sulfate. The crude product was employed in the next step without further purification. Yield: 98%

Step 2: The product just obtained in step 1 (171.3 mmol, 1 eq.) was dissolved in THF (250 ml), lithium aluminium hydride (342.6 mmol, 2 eq.) was added at 0° C. and the mixture was heated under reflux for 2 h. It was then cooled to 0° C., ice-water (100 g) was added, the mixture was diluted with ethyl acetate and the phases were separated. The aqueous phase was extracted with ethyl acetate. The combined organic phases were diluted with methylene chloride (100 ml), washed with dist. water and sat. NaCl solution and dried over sodium sulfate. The crude product was employed in the next step without further purification.

Yield: 82%

Step 3: The product just obtained in step 2 (139.5 mmol) was dissolved in methylene chloride (300 ml), PCC (209.3 mmol, 1.5 eq.) was added and the mixture was stirred at 25° C. for 16 h. The reaction mixture was filtered over Celite and washed with methylene chloride (2×200 ml) and the filtrate was concentrated. The crude product was purified by column chromatography (mobile phase 20% ethyl acetate in methylene chloride). Yield: 42%

Step 4: The product just obtained in step 3 (5.87 mmol, 1 eq.) was dissolved in THF (250 ml), methyl vinyl ketone (7.63 mmol, 1.3 eq.) and 3 N KOH in ethanol (7.7 ml) were added at 0° C. and the mixture was stirred at room temperature for 16 h. The solution was concentrated to 1/3 and acidified with 0.5 N HCl at 0° C. The aqueous phase was extracted with ethyl acetate (2×100 ml) and the combined organic phases were washed with dist. water and sat. NaCl solution and dried over sodium sulfate. The crude product was employed in the next step without further purification. Yield: 91%

Step 5: The product just obtained in step 4 (6.41 mmol, 1 eq.) was dissolved in ethanol (500 ml), 10% Pd/C (3.4 g) was added and hydrogenation was carried out at room temperature for 16 h. The mixture was finally filtered over Celite, the filtrate was concentrated and the crude product was purified by column chromatography. Yield: 38%

Step 6 & 7: Dimethylamine (29.9 mmol, 10 eq.) was added at 0° C. to a solution of the spiro-ketone just prepared in step 5 (2.99 mmol, 1 eq.) in methanol (15 ml) and acetic acid (1.5 ml). Potassium cyanide (7.47 mmol, 2.5 eq.) was added and the mixture was stirred for 16 h. NH₄OH solution (50 g of ice+50 ml of 25% strength ammonia solution) was cautiously added at 0° C. and the mixture was stirred for 30 minutes. The reaction mixture was extracted with ethyl acetate and the combined organic phases were washed with dist. water (15 ml), saturated iron sulfate solution (15 ml) and sat. NaCl solution (20 ml), dried over sodium sulfate and concentrated. This crude product (1.1 g crude) was dissolved in THF (30 ml), the solution was added dropwise to a bromo-(4-fluorophenyl)-magnesium solution (5 eq. of a 1 M solution in THF) at 0° C. and the mixture was stirred at room temperature under nitrogen for 16 h. Finally, saturated ammonia solution was added and the mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (25% ethyl acetate/hexane). Yield: 14%

Synthesis of Amine (AMN_CC-25) 8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carboxylic acid tert-butyl ester (AMN_CC-25)

BINAP (293 mg, 0.47 mmol) and Pd(OAc)₂ (317 mg, 1.4 mmol) was added to a mixture of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (5.66 g, 23.6 mmol), 4-bromopyridine HCl (4.58 g, 23.6 mmol) and sodium tert-butylate (6.8 g, 70.8 mmol) in toluene and the reaction mixture was degassed under argon for 20 minutes and heated under reflux for 4 h. The mixture was then diluted with ethyl acetate, stirred for 15 minutes and filtered over Celite. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 43.3%

Synthesis of Amine (AMN_CC-26) 2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester (AMN_CC-26)

BINAP (293 mg, 0.47 mmol) and Pd(OAc)₂ (317 mg, 1.4 mmol) was added to a mixture of 2,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester (5.66 g, 23.6 mmol), 4-bromopyridine HCl (4.58 g; 23.6 mmol) and sodium tert-butylate (6.8 g, 70.8 mmol) in toluene and the reaction mixture was degassed under argon for 20 minutes and heated under reflux for 4 h. The mixture was then diluted with ethyl acetate, stirred for 15 minutes and filtered over Celite. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 53%

3) Synthesis of the Acid Units (ACI_CC): Overview:

Unit no. Structure Unit name ACI_CC-20

3-[(4-methoxy-2,6-dimethyl-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid ACI_CC-21

3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H- indene-5-carboxylic acid ACI_CC-22

3-[(3-chloro-thiophene-2-carbonyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid ACI_CC-23

3-[(2-chloro-benzoyl)-methyl-amino]-2,3-dihydro- 1H-indene-5-carboxylic acid ACI_CC-24

3-[(2-chloro-benzoyl)-cyclopropyl-amino]-2,3- dihydro-1H-indene-5-carboxylic acid ACI_CC-25

9-[(2-chloro-benzoyl)amino]-6,7,8,9-tetrahydro- 5H-benzocycloheptene-2-carboxylic acid ACI_CC-26

3-[[(2-chloro-benzoyl)amino]-methyl]-2,3-dihydro- 1H-indene-5-carboxylic acid ACI_CC-27

2-[3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H- inden-5-yl]-acetic acid ACI_CC-28

3-(8-chloro-1-oxo-3,4-dihydro-2H-pyrrolo[1,2- a]pyrazin-2-yl)-2,3-dihydro-1H-indene-5- carboxylic acid ACI_CC-29

3-(8-chloro-4-methyl-1-oxo-3,4-dihydro-2H- pyrrolo[3,4-b]indol-2-yl)-2,3-dihydro-1H-indene- 5-carboxylic acid ACI_CC-30

3-(5-chloro-2-fluorobenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid ACI_CC-31

3-(2-chloro-5-(trifluoromethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylic acid ACI_CC-32

3-(2,3-dichlorobenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid ACI_CC-33

3-(2-chloro-6-methylbenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid ACI_CC-34

3-(2-chloro-6-fluorobenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid

Synthesis of Acid Unit (ACI_CC-20) 3-[(4-Methoxy-2,6-dimethyl-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-20)

Step 1: TFA (160 ml) was added dropwise to a solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester A (8 g, 27.49 mmol) in methylene chloride (200 ml) at 0° C. and the mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated and the desired TFA salt was obtained. Diisopropylamine (14 ml, 81.66 mmol) was added to a solution of 4-methoxy-2,6-dimethyl benzoic acid (4.9 g, 27.22 mmol), EDCI (10.39 g, 54.44 mmol) and HOBT (3.67 g, 27.22 mmol) in methylene chloride (125 ml) and the mixture was stirred at 0° C. for 10 minutes. A solution of the TFA salt just prepared in diisopropylamine (14 ml) and methylene chloride (125 ml) was then added and the mixture was stirred for 12 h. The reaction mixture was extracted with methylene chloride, the combined organic phases were washed with NH₄Cl solution, sodium hydrogen sulfate solution, water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate 20% in hexane). Yield: 49.95%

Step 2: The product just obtained in step 1 (5.3 g, 15.01 mmol) was dissolved in 265 ml of THF-methanol-water (3:1:1) and the solution was cooled to 0° C. Lithium hydroxide hydrate (1.89 g, 45.03 mmol) was added in portions and the mixture was stirred at room temperature for 8 h. The reaction mixture was then concentrated to dryness, the residue was taken up in a little dist. water and the mixture was washed with diethyl ether. HCl solution was added to the aqueous phase at 0° C. and the white solid formed was filtered out, washed with dist. water and dried in vacuo at 60° C. for 24 h. Yield: 84.50%

Synthesis of Acid Unit (ACI_CC-21) 3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-21)

The acid unit ACI_CC-21 corresponds to the acid unit E-01 already described.

Synthesis of Acid Unit (ACI_CC-22) 3-[(3-Chloro-thiophene-2-carbonyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-22)

Step 1: TFA (120 ml) was added dropwise to a solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester A (5.7 g, 19.58 mmol) in methylene chloride (150 ml) at 0° C. and the mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated and the desired TFA salt was obtained. Diisopropylamine (14 ml, 81.66 mmol) was added to a solution of 3-chloro-thiophene-2-carboxylic acid (2.6 g, 16.04 mmol), EDCI (6.13 g, 32.08 mmol) and HOBT (2.16 g, 16.04 mmol) in methylene chloride (50 ml) and the mixture was stirred at 0° C. for 10 minutes. A solution of the TFA salt just prepared in diisopropylamine (14 ml) and methylene chloride (50 ml) was then added and the mixture was stirred for 12 h. The reaction mixture was extracted with methylene chloride and the combined organic phases were washed with NH₄Cl solution, sodium hydrogen sulfate solution, water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate 20% in hexane). Yield: 65.13%

Step 2: The product just obtained in step 1 (3.11 g, 9.28 mmol) was dissolved in 150 ml of THF-methanol-water (6:3:1) and the solution was cooled to 0° C. Lithium hydroxide hydrate (1.16 g, 27.84 mmol) was added in portions and the mixture was stirred at room temperature for 8 h. The reaction mixture was then concentrated to dryness, the residue was taken up in a little dist. water and the mixture was washed with diethyl ether. HCl solution was added to the aqueous phase at 0° C. and the white solid formed was filtered out, washed with dist. water and dried in vacuo at 60° C. for 24 h. Yield: 96%

Synthesis of Acid Unit (ACI_CC-23) 3-[(2-Chloro-benzoyl)-methyl-amino]-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-23)

Step 1: NaH (2.05 g, 42.95 mmol) was added in portions to a solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (5 g, 17.18 mmol) in DMF (80 ml) at 0° C. and the mixture was then stirred at room temperature for 2 h. The reaction mixture was cooled to 0° C., methyl iodide (3.24 ml, 51.54 mmol) was added dropwise and the mixture was stirred at room temperature for 16 h. Hydrolysis was then carried out with ice and dist. water and the mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate/hexane). Yield: 61.75%

Step 2: The product just obtained in step 1 (4 g, 13.11 mmol) was dissolved in methylene chloride (200 ml), the solution was cooled to 0° C. and trifluoroacetic acid (100 ml) was added. The reaction mixture was stirred at room temperature for 4 h and then concentrated. The TFA salt of the splitting off of the Boc protective group was dissolved in methylene chloride (70 ml), the solution was cooled to 0° C. and diisopropylamine (22.6 ml, 70 mmol) was added. Thereafter, 2-chlorobenzene-acid chloride was added and the mixture was stirred at 20° C. for 12 h. The reaction mixture was extracted with methylene chloride and the combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate 20% in hexane). Yield: 89%

Step 3: The product just obtained in step 2 (3.5 g, 10.34 mmol) was dissolved in 150 ml of THF-methanol-water (3:1:1). LiOH.H₂O was added in portions at 0° C. (1.30 g, 31.02 mmol) and the mixture was stirred at room temperature for 8 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether. The aqueous phase was acidified with aqueous HCl solution at 0° C. A white solid precipitated out, which was filtered out, washed with water and dried in vacuo at 60° C. for 24 h. Yield: 96%

Synthesis of Acid Unit (ACI_CC-24) 3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-24)

Step 1: Cyclopropylamine (360 mg, 6.36 mmol) and acetic acid (315 mg, 5.26 mmol) were added to a solution of 3-oxo-1,2-dihydro-indene-5-carboxylic acid methyl ester (1 g, 5.26 mmol) in methylene chloride (25 ml) at 5-10° C. After stirring for 20 minutes, sodium triacetoxyborohydride (4.45 g, 21 mmol) was added and the mixture was warmed to room temperature and stirred for 16 h. Dist. water was then added, the mixture was stirred for a further 30 minutes, the phases were separated and the aqueous part was rendered basic with 10% strength NaOH solution and extracted with ethyl acetate. The combined organic phases washed with dist. water and sat. NaCl solution and dried over sodium sulfate. The crude product was employed in the next step without further purification. Yield: 25%

Step 2: The product just obtained in step 1 (300 mg, 1.29 mmol) was dissolved in methylene chloride (10 ml) and diisopropylamine (4 eq.) was added at 0° C. 2-Chlorobenzoyl chloride (340 mg, 1.97 mmol) was added and the mixture was stirred at room temperature for 16 h. The mixture was diluted with methylene chloride (10 ml) and then washed with dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. Yield: 62%

Step 3: The product just obtained in step 2 (3 g, 8.13 mmol) was dissolved in 50 ml of THF-methanol-water (6:3:1). LiOH.H₂O (1.50 g, 35 mmol, 4 eq.) was added in portions at 0° C. and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether and acidified with 10% citric acid solution to obtain the desired acid. Yield: 95%

Synthesis of Acid Unit (ACI_CC-25): 9-[(2-Chloro-benzoyl)amino]-6,7,8,9-tetrahydro-5H-benzocycloheptene-2-carboxylic (ACI_CC-25)

Step 1: NaH (60% strength in mineral oil, 1.5 g, 40 mmol) was added to a suspension of 4-formyl-benzoic acid methyl ester (3.2 g, 20 mmol) and (3-carboxy propyl)-triphenyl phosphonium bromide (8.6 g, 20 mmol) in 80 ml of DMSO/THF 1:1 and the mixture was stirred first at 0-5° C. for 30 minutes and then at room temperature for 6 h. Thereafter, the reaction mixture was cooled to 0° C., dist. water (10 ml) and 6 M HCl 10 ml) were added and the mixture was stirred for 20 minutes. The reaction mixture was extracted with ethyl acetate and the combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate 10% in hexane). Yield: 66% (3 g)

Step 2: 10% Pd/C was added to a solution of the product just obtained in step 2 (1 g, 4.27 mmol) in ethyl acetate/methylene chloride 2:1 and the mixture was degassed under argon. The reaction mixture was hydrogenated at 25° C. for 12 h, the catalyst was filtered out over Celite and the residue was rinsed with ethyl acetate. The filtrate was concentrated to dryness under reduced pressure and the combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. Yield: 100% (1 g)

Step 3: The product just obtained in step 2 (1 g, 4.2 mmol) was dissolved in 20 ml of THF-methanol-water (6:3:1). LiOH.H₂O (0.75 g, 17 mmol) was added in portions at 0° C. and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether and acidified with 10% strength citric acid in order to obtain the desired acid.

Yield: 72% (700 mg)

Step 4: A mixture of the product just obtained in step 3 (700 mg, 3.16 mmol), AlCl₃ (2.94 g, 22.17 mmol) and NaCl (295 mg, 3.2 mmol) was heated at 180° C. for 1 hour. It was then cooled to 100° C. and poured on to ice in portions. The reaction mixture was acidified with 6 M HCl and extracted with ethyl acetate and the combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. The combined organic phases were dried over sodium sulfate and concentrated under reduced pressure.

Yield: 31% (200 mg)

Step 5: H₂SO₄ (catalytic) was added to a solution of the product just obtained in step 4 (200 mg, 0.98 mmol) in methanol (8 ml) and the mixture was heated under reflux for 16 h. The organic phase was concentrated under reduced pressure and the crude product was purified by column chromatography. Yield: 51% (110 mg)

Step 6: Hydroxylamine (1.4 g, 20.6 mmol) and sodium acetate (3.4 g, 41.28 mmol) were added at room temperature to a solution of the product just obtained in step 5 (1.5 g, 6.88 mmol) in methanol (50 ml) and the mixture was then heated under reflux for 2 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in ethyl acetate and the mixture was washed with dist. water and sat. NaCl solution. The organic phase was dried over sodium sulfate and concentrated in order to obtain the crude product.

Yield: 90% (1.4 g)

Step 7: Dist. water (3.5 ml) and conc. HCl (7.2 ml) were added to a solution of the product just obtained in step 6 (1.2 g, 5.15 mmol) in ethanol (15 ml) and the mixture was stirred for 15 minutes. The reaction mixture was cooled, Zn powder (2 g, 31 mmol) was slowly added and the mixture was then heated under reflux for 1 hour. After it had cooled to room temperature, it was filtered over Celite and the residue was rinsed with ethanol. The filtrate was concentrated, the residue was taken up again in toluene and the mixture was concentrated to dryness again in order to obtain the desired crude amine. The crude amine (4 g) was dissolved in 1,4-dioxane (12 ml) and the solution was cooled to 0° C. Triethylamine (2 eq.) and Boc anhydride (3.98 g, 18.2 mmol) were added and the mixture was stirred at room temperature for 12 h. The 1,4-dioxane was concentrated under reduced pressure and the residue was taken up in ethyl acetate and water (50 ml of each). The phases were separated and the organic phase was washed with dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 85% (1.6 g)

Step 8: A solution of the product just obtained in step 7 (1.8 g, 5.6 mmol) in methylene chloride (25 ml) was cooled to 0° C., trifluoroacetic acid (2.5 ml) was added and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated to dryness under reduced pressure (TFA salt). The TFA salt was dissolved in methylene chloride, the solution was cooled to 0° C. and diisopropylamine (4 eq.) was added. 2-Chlorobenzoyl chloride (1.5 eq.) was added and the mixture was stirred at room temperature for 4 h. The reaction mixture was diluted with methylene chloride and washed with dist. water and sat. NaCl solution, and the organic phase was dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate 20% in hexane). Yield: 80% (1.6 g)

Step 9: LiOH.H₂O (2.4 g, 56 mmol, 4 eq.) was added at 0° C. to a solution of the product just obtained in step 8 (5 g, 14 mmol) in 75 ml of THF-methanol-water (6:3:1) and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether and acidified with 10% strength citric acid in order to obtain the desired acid in the form of a white solid. Yield: 62%

Synthesis of Acid Unit (ACI_CC-26) 3-[[(2-Chloro-benzoyl)amino]-methyl]-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-26)

Step 1: NaH (6.31 g, 0.15 mol) was added to a solution of methoxymethyl triphenylphosphorus chloride (36 g, 0.10 mol) in THF (400 ml) at 0° C. and the mixture was stirred for 30 minutes. 3-Oxo-1,2-dihydro-indene-5-carboxylic acid methyl ester (10 g, 0.052 mmol) was dissolved in THF (50 ml) and added, and the mixture was stirred at room temperature for 16 h. Ethyl acetate was added and the organic phase was washed with sat. NH₄Cl solution, dist. water and sat. sodium chloride solution and dried over sodium sulfate. The organic phase was concentrated under reduced pressure and the residue was purified by column chromatography (mobile phase: methanol/methylene chloride). The ether intermediate (6.9 g) was obtained. This intermediate was dissolved in acetone (100 ml), 6 M HCl (20 ml) was added and the mixture was stirred at 50° C. for 3 h. The reaction mixture was concentrated under reduced pressure and the residue was neutralized with sodium bicarbonate solution. The aqueous phase was extracted with methylene chloride and the combined organic phases were washed with sat. NH₄Cl solution, dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated to dryness under reduced pressure. The crude product was employed in the next step without further purification. Yield: 56%

Step 2: Hydroxylamine HCl (4.7 g, 67.74 mmol) and Amberlyst-A-21 resin (23 g) were added at room temperature to a solution of the product just obtained in step 1 (4.6 g, 22.54 mmol) in methanol (50 ml) and the mixture was heated under reflux for 2 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate/hexane). Yield: 93%

Step 3 & 4: Dist. water (11 ml) and conc. HCl (24 ml) was added to a solution of the product just obtained in step 2 (4.6 g, 0.21 mol) in ethanol (50 ml) and the mixture was stirred for 15 minutes. The reaction solution was cooled, Zn powder (7.36 g, 112 mmol) was slowly added and the mixture was then refluxed for 1 hour. The reaction mixture was cooled to room temperature and filtered over Celite, the residue was rinsed with ethanol and the filtrate was concentrated under reduced pressure. The residue was taken up in toluene and the mixture was concentrated to dryness again. The crude product (amine) was dissolved in methylene chloride (100 ml), the solution was cooled to 0° C., triethylamine (4 ml, 29.5 mmol) and 2-chlorobenzoyl chloride (4.1 g, 23.4 mmol) were added and the mixture was stirred at room temperature for 2 h. Dist. water was added, the phases were separated and the organic phase was washed with dist. water, sat. sodium bicarbonate solution and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase ethyl acetate/hexane). Yield: 56%

Step 5: LiOH.H₂O (1.17 g, 27.98 mmol) was added in portions at 0° C. to a solution of the product just obtained in step 4 (2.4 g, 6.997 mmol) in 40 ml of THF-methanol-water (6:4:1) and the mixture was stirred at room temperature for 8 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether. The aqueous phase was acidified with 2 M HCl at 0° C., during which a white solid precipitated out. This was filtered out, washed with water and dried at 60° C. for 24 h.

Yield: 87%

Synthesis of Acid Unit (ACI_CC-27) 2-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-inden-5-yl]-acetic acid (ACI_CC-27)

Step 1: A solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (to which acetic acid tert-butyl ester was added) (10 g, 34.36 mmol) in THF (50 ml) was added dropwise to a suspension of lithium aluminium hydride (1.56 g, 41.23 mmol) in THF (40 ml) at 0° C. and the mixture was then stirred at room temperature for 2 h. The reaction was quenched with sat. sodium sulfate solution, the mixture was filtered over Celite and the residue was rinsed with THF. The filtrate was concentrated to dryness in order to obtain the desired product. Yield: 62% (7.7 g)

Step 2: Triethylamine (6.1 ml, 45.05 mmol) was added to a solution of the product just obtained in step 1 (7.9 g, 30.03 mmol) in methylene chloride (150 ml) and the mixture was then cooled to −20° C. Methanesulfonyl chloride (4.2 ml, 36.03 mmol) was added dropwise and the reaction mixture was stirred for one hour. The mixture was diluted with methylene chloride and washed with dist. water & sat. NaCl solution. The organic phase was dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate/hexane). Yield: 97%

Step 3: LiBr (5 g, 58.65 mmol) was added at room temperature to a solution of the product just obtained in step 2 (10 g, 29.32 mmol) in acetone (150 ml) and the mixture was heated under reflux for 2 h. The reaction mixture was cooled to room temperature and filtered over Celite, the filtrate was concentrated and the residue was taken up in ethyl acetate. The organic phase was washed with dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. Yield: 93%

Step 4: KCN (3.55 g, 54.6 mmol) was added at room temperature to a solution of the product just obtained in step 3 (8.9 g, 27.3 mmol) in DMF (190 ml). The reaction mixture was heated at 100° C. for 16 h. It was then cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. Yield: 44%

Step 5 & 6: 1 N NaOH (64.4 ml, 64.3 mmol)) was added to a solution of the product just obtained in step 4 (7 g, 25.73 mmol) in ethanol (250 ml) and the mixture was refluxed for 16 h. It was then cooled to room temperature and concentrated under reduced pressure. The residue was taken up in dist. water and the mixture was extracted with ethyl acetate. The aqueous phase was acidified with citric acid and extracted with ethyl acetate. The organic phase was washed with dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was dissolved in acetone (50 ml), potassium carbonate (4 g) was added, the mixture was cooled to 0° C., methyl iodide (1.7 ml, 27 mmol) was added and the mixture was stirred at room temperature for 16 h. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (mobile phase ethyl acetate/hexane). Yield: 20%

Step 7 & 8: Trifluoroacetic acid (18 ml) was added to a solution of the product just obtained in step 6 (900 mg, 2.95 mmol) in methylene chloride (50 ml) and the mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in methylene chloride (20 ml) and triethylamine (1.2 ml, 8.85 mmol), 2-chlorobenzoyl chloride (0.45 ml, 3.54 mmol) was added and the mixture was stirred at room temperature for 1 hour. Dist. water was added to the reaction mixture and the phases were separated. The organic phase was washed with dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase ethyl acetate/hexane). Yield: 49%

Step 9: LiOH.H₂O (0.167 g, 5.83 mmol) was added in portions at 0° C. to a solution of the product just obtained in step 6 (0.5 g, 1.457 mmol) in 15 ml of THF-methanol-water (6:4:1) and the mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether. The aqueous phase was acidified with 2 M HCl at 0° C., during which a white solid precipitated out. This was filtered out, washed with water and dried at 60° C. for 24 h. Yield: 74%

Synthesis of Acid Unit (ACI_CC-28) 3-(8-Chloro-1-oxo-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-28)

Step 1: 5-Methyl-3,4-dihydro-2H-pyrrole (24.06 mmol, 1 eq.) was dissolved in CCl₄ and N-chlorosucdinimide (8 eq.) was added in portions at 0° C. The suspension was refluxed for 3 days, the reaction mixture was then cooled to 0° C. and the succinimide was filtered out and rinsed with carbon tetrachloride. The filtrate was concentrated to dryness under reduced pressure. The crude product was employed in the next step without further purification. Yield: 90%

Step 2: The product just obtained in step 1 (27.31 mmol) was added to a solution of sodium methanolate in methanol (2 M, 6 eq.) and the mixture was heated under reflux for 1.5 h. After cooling to room temperature, the solvent was distilled off under reduced pressure. The residue was taken up in ether (10 ml) and the mixture was stirred at room temperature for 30 minutes. The precipitate obtained was filtered out and the filtrate was dried over potassium carbonate and concentrated under reduced pressure. This residue was taken up in 2 M HCl and the mixture was extracted with methylene chloride (3×). The combined organic phases were dried over sodium sulfate and concentrated to dryness. The crude product was employed in the next step without further purification. Yield: 83%

Step 3: The product just obtained in step 2 (4.32 g, 27 mmol) was dissolved in 110 ml of THF-methanol-water (6:4:1), LiOH.H₂O (3.42 g, 81 mmol) was added in portions at 0° C. and the mixture was stirred at room temperature for 8 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether and acidified with 10% strength citric acid at 0° C. in order to obtain the desired acid in the form of a white solid. This was filtered out, washed with water and dried at 60° C. for 24 h. Yield: 77%

Step 4: The product just obtained in step 3 (1.287 mmol/1 eq.) was dissolved in DMF (6 ml), BOP reagent (2.57 mmol, 2 eq.) and N-methylmorpholine (3.86 mmol, 3 eq.) were added and the mixture was stirred at room temperature for 15 minutes. A solution of 3-amino-2,3-dihydro-1H-indene-5-carboxylic acid tert-butyl ester (1.287 mmol, 1 eq.) in DMF (1 ml) was added and the mixture was stirred at room temperature for 12 h. The reaction mixture was poured on to dist. water and the mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 59%

Step 5: 1,2-Dibromoethane (21.66 mmol, 10 eq.) was added to a mixture of the product just obtained in step 4 (21.6 mmol, 1 eq.) and tetrabutylammonium bromide (1 eq.) in 1 M NaOH (13 ml) and the mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with dist. water and the mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 95%

Step 6: The product obtained in step 5 (1.554 mmol) was dissolved in methylene chloride (10 ml), the solution was cooled to 0° C. and trifluoroacetic acid (2.1 ml) was added. The mixture was stirred at room temperature for 6 h. The solvent was removed under reduced pressure, dist. water was added to the residue and the mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 96%

Synthesis of Acid Unit (ACI_CC-29) 3-(8-Chloro-4-methyl-1-oxo-3,4-dihydro-2H-pyrrolo[3,4-b]indol-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-29)

Step 1: Methyl acetoacetate (59.82 mmol, 2.1 eq.) was added dropwise to a suspension of NaH (65.52 mmol, 23 eq.) in DMF (40 ml) at 0° C. The mixture was stirred for 10 minutes, 1-chloro-2-fluoro-3-nitro-benzene (28.49 mmol, 1 eq.) was added and the mixture was finally stirred at room temperature for 16 h. 2 M HCl and water were added to the reaction mixture and the mixture was extracted with diethyl ether. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 51%

Step 2: The product just obtained in step 1 (14.76 mmol) was dissolved in acetic acid (96 ml), a 20% strength TiCl₃ solution (20%—w/w in 2 N HCl, 71.6 ml) was added and the mixture was heated at 90° C. for 5-10 minutes. The reaction mixture was then cooled in an ice bath, and water and methylene chloride/methanol (9:1) were added. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was titrated with hexane in order to obtain the desired product in a pure form. Yield: 53%

Step 3: A solution of the product obtained in step 2 (13.45 mmol, 1 eq.) in DMF (70 ml) was added to a suspension (0° C.) of NaH (26.90 mmol, 2 eq.) in DMF (13 ml) and the mixture was stirred for 30 minutes. Methyl iodide (20.17 mmol, 1.5 eq.) was added dropwise at 0° C. and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with NH₄Cl solution and extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. Yield: 60%

Step 4: The product just obtained in step 3 (9.70 mmol, 1 eq.) was dissolved in carbon tetrachloride (97 ml), NBS (9.70 mmol, 1 eq.) and benzoyl peroxide (0.19 mmol, 0.02 eq.) were added and the mixture was stirred at 85° C. for 1 hour. The precipitate formed was filtered out and the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 51%

Step 5: Triethylamine (10.59 mmol, 1.2 eq.) was added to a solution of the product just obtained in step 4 (8.83 mmol, 1.0 eq.) and 3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester A (8.83 mmol, 1.0 eq.) in benzene (36 ml) and the mixture was heated under reflux for 16 h. The reaction mixture was then diluted with ethyl acetate and the organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 80%

Step 6: The product just obtained in step 5 (5.59 mmol, 1 eq.) was dissolved in methylene chloride (38 ml), the solution was cooled to 0° C., AlMe₃ (2 M solution in toluene, 2.0 eq.) was added under an inert gas atmosphere and the mixture was stirred for 10 minutes in the cold and 2 h at room temperature. The reaction mixture was quenched with 2 N HCl, while cooling, and diluted with methylene chloride. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was titrated with ethyl acetate in order to obtain the desired product in a pure form. Yield: 75%

Step 7: The product just obtained in step 6 (2.25 mmol, 1 eq.) was dissolved in methanol (34 ml), 3 M NaOH (3.3 ml.) was added and the mixture was heated under reflux for 15 h. Methanol was removed under reduced pressure, the residue was diluted with dist. water and the mixture was acidified with 1 M HCl. The precipitate formed was filtered out and dried. The crude product was employed in the next step without further purification. Yield: 96%

Synthesis of Acid Unit (ACI_CC-30) 3-(5-chloro-2-fluorobenzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-30)

Step 1: Methyl 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylate (25.3 g, 80 mmol) was dissolved in ethanol (280 ml) and cooled to 0° C. Acetylchloride (28.3 ml) was added, the reaction mixture was stirred at room temperature over night and finally concentrated under reduced pressure. Yield: 69.5 mmol/86.9%

Step 2: 5-Chloro-2-fluoro benzoic acid (5.0 g, 28.6 mmol), 1-Hydroxybenzotriazole hydrate (0.90 g, 6.87 mmol) and N,N-diisopropylethylamine (15.6 ml, 91.6 mmol) were dissolved in methylene chloride (600 ml) and the solution cooled to 0° C. 1-(3-Dimethylaminopropyl)-3-ethylcarbdiimide hydrochloride (6.57 g, 34.4 mmol) was added and the solution stirred for at least 15 minutes before the amine hydrochloride obtained in step 1 (5.22 g, 22.9 mmol) was added and the mixture stirred at room temperature over night. The reaction mixture was washed three times with 0.5 M aqueous KOH solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: methylene chloride/methanol). Yield: 25.2 mmol/110%

Step 3: The product obtained in step 2 (8.76 g, 25.2 mmol) was dissolved in 185 ml of methanol-water-THF (3:1:2) and cooled to 0° C. LiOH 2H₂O (1.20 g, 50.4 mmol) was added and the mixture was stirred at room temperature over night. The reaction mixture was then heatet to 60° C. for 3 h. After cooling to room temperature the mixture was concentrated under reduced pressure, the residue was taken up in water and washed with ether. The aqueous phase was acified with 1 M aqueous HCl. A white solid precipitated, which was filtered out, washed with water and dried in vacuo. Yield: 25.5 mmol/101%

Synthesis of Acid Unit (ACI_CC-31) 3-(2-chloro-5-(trifluoromethyl)benzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-31)

Step 1: See step 1 of acid unit ACI_CC-30

Yield: 69.5 mmol/86.9%

Step 2: The amine hydrochloride obtained in step 1 (4.53 g, 17.15 mmol) was suspended in methylene chloride (66 ml) and then cooled to 0° C. under nitrogen. Triethylamine (7.12 ml, 51.5 mmol) and 2-Chloro-5-(trifluoromethyl)benzoyl chloride (5.00 g, 20.6 mmol) were added and the solution was stirred for 2 hours at room temperature. The reaction mixture was diluted with methylene chloride and washed with water and brine, dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: methylene chloride/methanol). Yield: 19.1 mmol/111%

Step 3: In analogy to step 3 of acid unit ACI_CC-30

Yield: 18.6 mmol/97.8%

Synthesis of Acid Unit (ACI_CC-32) 3-(2,3-dichlorobenzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-32)

Step 1: See step 1 of acid unit ACI_CC-30

Yield: 69.5 mmol/86.9%

Step 2: In analogy to step 2 of acid unit ACI_CC-31 utilizing 2,3-Dichlorobenzoyl chloride

Yield: 22.7 mmol/114%

Step 3: In analogy to step 3 of acid unit ACI_CC-30

Yield: 22.4 mmol/98.9%

Synthesis of Acid Unit (ACI_CC-33): 3-(2-chloro-6-methylbenzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-33)

Step 1: See step 1 of acid unit ACI_CC-30

Yield: 69.5 mmol/86.9%

Step 2: In analogy to step 2 of acid unit ACI_CC-30 utilizing 2-Chloro-6-methyl benzoic acid

Yield: 17.8 mmol/70.4%

Step 3: In analogy to step 3 of acid unit ACI_CC-30

Yield: 17.1 mmol/96.3%

Synthesis of Acid Unit (ACI_CC-34) 3-(2-chloro-6-fluorobenzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-34)

Step 1: See step 1 of acid unit ACI_CC-30

Yield: 69.5 mmol/86.9%

Step 2: In analogy to step 2 of acid unit ACI_CC-31 utilizing 2-Chloro-6-fluorobenzoyl chloride

Yield: 20.2 mmol/93.8%

Step 3: In analogy to step 3 of acid unit ACI_CC-30

Yield: 19.8 mmol/97.8%

4) Parallel Synthesis General:

The amine units AMN_CC′ were prepared from the Boc-protected amines AMN_CC by Parallel Method 1 in accordance with the above equation. The amine trifluoroacetic acid salts AMN_CC′ obtained in this way were reacted in parallel synthesis by Parallel Method 2 with the acids ACI_CC to give the amidic products IND_CC. The correlation of products (IND_CC) to the units used (ACI_CC) and can be seen from the synthesis matrix. The crude products of the parallel synthesis were purified by column chromatography. It was possible to demonstrate the identity of the products by analytical HPLC-MS measurements (cf. HPLC-MS data).

Parallel Method 1: Boc Deprotection

20% trifluoroacetic acid in methylene chloride (10 ml/mol) was added to the corresponding Boc-protected amine (1 eq., AMN_CC) at 0° C. The reaction mixture obtained was stirred at 25° C. for 4 h. The course of the reaction was monitored by means of thin layer chromatography. The solvent was then removed under reduced pressure and the residue was dried thoroughly in order to remove traces of trifluoroacetic acid. The crude product obtained in this way was used for synthesis of the libraries without further purification.

Parallel Method 2: Amide Formation

HATU (2 eq.) was added to a methylene chloride solution (3 ml/mmol) of the acid unit ACI_CC (1 eq.) at 0° C. and the mixture was stirred for 15 min. In a further round-bottomed flask, a methylene chloride solution (1 ml/mmol) of the Boc-deprotected amine unit AMN_CC′ (1.5 eq.) was cooled in an ice bath, DIPEA (3 eq.) was added and the mixture was then added to the acid unit at 0° C. The reaction mixture was stirred at room temperature for 16 h and finally diluted with methylene chloride. The organic phase was washed successively with aqueous NH₄Cl solution, NaHCO₃ solution and sat. NaCl solution, dried over Na₂SO₄ and concentrated under reduced pressure. The crude product was purified via a Biotage parallel purification system. Some compounds were purified manually by column chromatography over neutral aluminium oxide with methanol/methylene chloride as the mobile phase. A few compounds were purified via prep. HPLC with an aqueous ammonia method.

Synthesis Matrix:

Example no. ACI_CC Amine (AMN_CC) Method no. Ind_CC-090 ACI_CC-20 AMN_CC-21 No. 1 & No. 2 Ind_CC-091 ACI_CC-20 AMN_CC-22 No. 1 & No. 2 Ind_CC-092 ACI_CC-20 AMN_CC-23 No. 1 & No. 2 Ind_CC-093 ACI_CC-20 AMN_CC-24 No. 1 & No. 2 Ind_CC-094 ACI_CC-20 AMN_CC-26 No. 1 & No. 2 Ind_CC-095 ACI_CC-21 AMN_CC-20 No. 1 & No. 2 Ind_CC-096 ACI_CC-21 AMN_CC-21 No. 1 & No. 2 Ind_CC-097 ACI_CC-21 AMN_CC-22 No. 1 & No. 2 Ind_CC-098 ACI_CC-21 AMN_CC-23 No. 1 & No. 2 Ind_CC-099 ACI_CC-21 AMN_CC-24 No. 1 & No. 2 Ind_CC-100 ACI_CC-21 AMN_CC-25 No. 1 & No. 2 Ind_CC-101 ACI_CC-21 AMN_CC-26 No. 1 & No. 2 Ind_CC-102 ACI_CC-22 AMN_CC-21 No. 1 & No. 2 Ind_CC-103 ACI_CC-22 AMN_CC-22 No. 1 & No. 2 Ind_CC-104 ACI_CC-22 AMN_CC-23 No. 1 & No. 2 Ind_CC-105 ACI_CC-22 AMN_CC-24 No. 1 & No. 2 Ind_CC-106 ACI_CC-23 AMN_CC-20 No. 1 & No. 2 Ind_CC-107 ACI_CC-23 AMN_CC-21 No. 1 & No. 2 Ind_CC-108 ACI_CC-23 AMN_CC-22 No. 1 & No. 2 Ind_CC-109 ACI_CC-23 AMN_CC-23 No. 1 & No. 2 Ind_CC-110 ACI_CC-23 AMN_CC-24 No. 1 & No. 2 Ind_CC-111 ACI_CC-23 AMN_CC-25 No. 1 & No. 2 Ind_CC-112 ACI_CC-23 AMN_CC-26 No. 1 & No. 2 Ind_CC-113 ACI_CC-24 AMN_CC-20 No. 1 & No. 2 Ind_CC-114 ACI_CC-24 AMN_CC-21 No. 1 & No. 2 Ind_CC-115 ACI_CC-24 AMN_CC-22 No. 1 & No. 2 Ind_CC-116 ACI_CC-24 AMN_CC-23 No. 1 & No. 2 Ind_CC-117 ACI_CC-24 AMN_CC-24 No. 1 & No. 2 Ind_CC-118 ACI_CC-24 AMN_CC-25 No. 1 & No. 2 Ind_CC-119 ACI_CC-24 AMN_CC-26 No. 1 & No. 2 Ind_CC-120 ACI_CC-25 AMN_CC-20 No. 1 & No. 2 Ind_CC-121 ACI_CC-25 AMN_CC-21 No. 1 & No. 2 Ind_CC-122 ACI_CC-25 AMN_CC-22 No. 1 & No. 2 Ind_CC-123 ACI_CC-25 AMN_CC-23 No. 1 & No. 2 Ind_CC-124 ACI_CC-25 AMN_CC-24 No. 1 & No. 2 Ind_CC-125 ACI_CC-25 AMN_CC-25 No. 1 & No. 2 Ind_CC-126 ACI_CC-25 AMN_CC-26 No. 1 & No. 2 Ind_CC-127 ACI_CC-26 AMN_CC-20 No. 1 & No. 2 Ind_CC-128 ACI_CC-26 AMN_CC-21 No. 1 & No. 2 Ind_CC-129 ACI_CC-26 AMN_CC-22 No. 1 & No. 2 Ind_CC-130 ACI_CC-26 AMN_CC-23 No. 1 & No. 2 Ind_CC-131 ACI_CC-26 AMN_CC-24 No. 1 & No. 2 Ind_CC-132 ACI_CC-26 AMN_CC-25 No. 1 & No. 2 Ind_CC-133 ACI_CC-26 AMN_CC-26 No. 1 & No. 2 Ind_CC-134 ACI_CC-27 AMN_CC-20 No. 1 & No. 2 Ind_CC-135 ACI_CC-27 AMN_CC-21 No. 1 & No. 2 Ind_CC-136 ACI_CC-27 AMN_CC-22 No. 1 & No. 2 Ind_CC-137 ACI_CC-27 AMN_CC-23 No. 1 & No. 2 Ind_CC-138 ACI_CC-27 AMN_CC-24 No. 1 & No. 2 Ind_CC-139 ACI_CC-27 AMN_CC-25 No. 1 & No. 2 Ind_CC-140 ACI_CC-27 AMN_CC-26 No. 1 & No. 2 Ind_CC-141 ACI_CC-28 AMN_CC-20 No. 1 & No. 2 Ind_CC-142 ACI_CC-28 AMN_CC-21 No. 1 & No. 2 Ind_CC-143 ACI_CC-28 AMN_CC-22 No. 1 & No. 2 Ind_CC-144 ACI_CC-28 AMN_CC-23 No. 1 & No. 2 Ind_CC-145 ACI_CC-28 AMN_CC-24 No. 1 & No. 2 Ind_CC-146 ACI_CC-28 AMN_CC-25 No. 1 & No. 2 Ind_CC-147 ACI_CC-28 AMN_CC-26 No. 1 & No. 2 Ind_CC-148 ACI_CC-29 AMN_CC-20 No. 1 & No. 2 Ind_CC-149 ACI_CC-29 AMN_CC-21 No. 1 & No. 2 Ind_CC-150 ACI_CC-29 AMN_CC-22 No. 1 & No. 2 Ind_CC-151 ACI_CC-29 AMN_CC-23 No. 1 & No. 2 Ind_CC-152 ACI_CC-29 AMN_CC-24 No. 1 & No. 2 Ind_CC-153 ACI_CC-29 AMN_CC-25 No. 1 & No. 2 Ind_CC-154 ACI_CC-29 AMN_CC-26 No. 1 & No. 2

Analytical Data:

Example no. [M+] found R.t. [min] Ind_CC-090 553.4 2.74 Ind_CC-091 570.4 2.87 Ind_CC-092 567.4 2.37 Ind_CC-093 612.5 2.85 Ind_CC-094 539.4 2.7 Ind_CC-095 529.2 2.69 Ind_CC-096 529.2 2.71 Ind_CC-097 546.3 6.51 Ind_CC-098 543.4 2.23 Ind_CC-099 588.4 2.81 Ind_CC-100 515.2 2.65 Ind_CC-101 515.2 2.66 Ind_CC-102 535.2 2.77 Ind_CC-103 552.3 6.89 Ind_CC-104 549.4 2.42 Ind_CC-105 594.4 2.87 Ind_CC-106 543.4 2.76 Ind_CC-107 543.4 2.77 Ind_CC-108 560.4 2.91 Ind_CC-109 557.4 2.4 Ind_CC-110 602.4 2.86 Ind_CC-111 529.2 2.72 Ind_CC-112 529.2 2.73 Ind_CC-113 569.4 2.83 Ind_CC-114 569.2 2.85 Ind_CC-115 586.4 3.03 Ind_CC-116 583.4 2.6 Ind_CC-117 628.4 2.96 Ind_CC-118 555.2 2.8 Ind_CC-119 555.2 2.81 Ind_CC-120 557.4 2.77 Ind_CC-121 557.4 2.79 Ind_CC-122 574.4 2.93 Ind_CC-123 571.4 2.49 Ind_CC-124 616.4 2.89 Ind_CC-125 543.2 2.73 Ind_CC-126 543.1 6.22 Ind_CC-127 543.2 2.77 Ind_CC-128 543.2 2.76 Ind_CC-129 560.4 2.9 Ind_CC-130 557.4 2.32 Ind_CC-131 557.4 2.88 Ind_CC-132 529.2 2.7 Ind_CC-133 529.2 2.7 Ind_CC-134 543.2 2.72 Ind_CC-135 543.2 2.72 Ind_CC-136 560.2 2.86 Ind_CC-137 557.4 1.7 Ind_CC-138 602.4 2.83 Ind_CC-139 529.2 2.2 Ind_CC-140 529.2 2.7 Ind_CC-141 544.2 2.69 Ind_CC-142 544.2 2.71 Ind_CC-143 561.2 2.82 Ind_CC-144 558.4 2.22 Ind_CC-145 603.4 2.83 Ind_CC-146 530.2 2.62 Ind_CC-147 530.2 2.65 Ind_CC-148 594.2 2.78 Ind_CC-149 594.2 2.79 Ind_CC-150 611.3 2.94 Ind_CC-151 608.4 2.57 Ind_CC-152 653.6 2.88 Ind_CC-153 580.4 2.76 Ind_CC-154 580.2 2.76

F) Parallel Synthesis Library No. 3: 1) Synthesis of the Secondary Amine Units (ASN_CC): Overview:

Unit no. Structure Unit name ASN_CC-01

2-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide (ASN_CC-01) ASN_CC-02

2-Chloro-N-[6-(3,9-diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide (ASN_CC-02) ASN_CC-03

N-[6-(3,8-Diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethyl- benzamide (ASN_CC-03) ASN_CC-04

3-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene- 2-carboxylic acid amide (ASN_CC-04) ASN_CC-05

2-Chloro-N-cyclopropyl-N-[6-(3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro- 1H-inden-1-yl]-benzamide (ASN_CC-05) ASN_CC-06

2-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-N-methyl- benzamide (ASN_CC-06) ASN_CC-07

5-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-fluoro- benzamide (ASN_CC-07) ASN_CC-08

5-Chloro-N-[6-(3,9-diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-fluoro- benzamide (ASN_CC-08) ASN_CC-09

2-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-5- (trifluoromethyl)-benzamide (ASN_CC-09) ASN_CC-10

2-Chloro-N-[6-(3,9-diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-5- (trifluoromethyl)-benzamide (ASN_CC-10) ASN_CC-11

2,3-Dichloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide (ASN_CC-11) ASN_CC-12

2,3-Dichloro-N-[6-(3,9-diazaspiro[5.5]undecane- 3-carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (ASN_CC-12) ASN_CC-13

2-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-methyl- benzamide (ASN_CC-13) ASN_CC-14

2-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-fluoro- benzamide (ASN_CC-14) ASN_CC-15

2-Chloro-N-[6-(3,9-diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-fluoro- benzamide (ASN_CC-15) ASN_CC-16

2-Chloro-N-[2-(3,8-diazaspiro[4.5]decane-3- carbonyl)-6,7,8,9-tetrahydro-5H- benzocyclohepten-9-yl]-benzamide (ASN_CC-16) ASN_CC-17

2-Chloro-N-[[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]- benzamide (ASN_CC-17) ASN_CC-18

8-Chloro-2-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-methyl- 3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one (ASN_CC-18) ASN_CC-19

8-Chloro-2-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro- 2H-pyrrolo[1,2-a]pyrazin-1-one (ASN_CC-19) ASN_CC-20

2-Chloro-N-[6-[2-(2,8-diazaspiro[4.5]decan-2-yl)- 2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (ASN_CC-20)

General Procedure for the Synthesis of the Secondary Amine Units (ASN_CC):

Step 1: 1-Hydroxybenzotriazole hydrate (0.35 g, 2.62 mmol), the corresponding acid (I) (3.5 g, 10.5 mmol) and N,N-diisopropylethylamine (3.0 ml, 17.5 mmol) were dissolved in methylene chloride (230 ml) and cooled to 0° C. 1-(3-Dimethylaminopropyl)-3-ethylcarbdiimide hydrochloride (2.51 g, 13.1 mmol) was added and the reaction mixture stirred for at least 15 minutes before the desired secondary amine (II) (2.1 g, 8.74 mmol) was added. Stirring was continued at room temperature over night. The reaction mixture was washed three times with 0.5 M aqueous KOH solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product (III) was purified by column chromatography (methylene chloride/methanol).

Step 2: Boc protected amine (III) (4.55 g, 8.18 mmol) was dissolved in ethanol (40 ml) and cooled to 0° C. Acetylchloride (2.9 ml) was added, the reaction mixture was stirred at room temperature over night and afterwards concentrated under reduced pressure. The obtained amine hydrochloride (IV) was used in the next step without further purification.

Step 3: Amine hydrochloride (IV) (4.26 g, 8.06 mmol) was dissolved in water, 1 M NaOH was added until pH 9 has been reached and extracted with methylene chloride. The organic layer was dried over sodium sulfate and concentrated under reduced pressure.

All secondary amine units (ASN_CC) depicted in the following table were synthesized according to the general procedure described above.

Unit no Structure Unit name Acid (ACI_CC) Amine (AMN) Yield ASN_CC-01

2-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzamide (ASN_CC-01) (ACI_CC-21) tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate Step 1: 96% (7.27 mmol) Step 2: 106% (7.62 mmol) Step 3: 90% (6.84 mmol) ASN_CC-02

2-Chloro-N-[6-(3,9- diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzamide (ASN_CC-02) (ACI_CC-21) tert-butyl 3,9- diazaspiro[5.5] undecane-3- carboxylate Step 1: 100% (7.83 mmol) Step 2: 105% (7.12 mmol) Step 3: 95% (6.79 mmol) ASN_CC-03

N-[6-(3,8- Diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-4-methoxy-2,6- dimethyl-benzamide (ASN_CC-03) (ACI_CC-20) tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate Step 1: 97% (7.71 mmol) Step 2: 101% (7.77 mmol) Step 3: 101% (7.83 mmol) ASN_CC-04

3-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-thiophene-2- carboxylic acid amide (ASN_CC-04) (ACI_CC-22) tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate Step 1: 91% (7.83 mmol) Step 2: 106% (8.66 mmol) Step 3: 93% (8.09 mmol) ASN_CC-05

2-Chloro-N-cyclopropyl-N-[6- (3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzamide (ASN_CC-05) (ACI_CC-24) tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate Step 1: 90% (5.86 mmol) Step 2: 104% (6.07 mmol) Step 3: 96% (5.81 mmol) ASN_CC-06

2-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-N-methyl- benzamide (ASN_CC-06) (ACI_CC-23) tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate Step 1: 80% (5.86 mmol) Step 2: 104% (6.91 mmol) Step 3: 102% (7.04 mmol) ASN_CC-07

5-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-2-fluoro- benzamide (ASN_CC-07) (ACI_CC-30) tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate Step 1: 94% (8.19 mmol) Step 2: 98% (8.06 mmol) Step 3: 99% (7.97 mmol) ASN_CC-08

5-Chloro-N-[6-(3,9- diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-2-fluoro- benzamide (ASN_CC-08) (ACI_CC-30) tert-butyl 3,9- diazaspiro[5.5] undecane-3- carboxylate Step 1: 78% (6.81 mmol) Step 2: 100% (6.83 mmol) Step 3: 100% (6.81 mmol) ASN_CC-09

2-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-5-(trifluoromethyl)- benzamide (ASN_CC-09) (ACI_CC-31) tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate Step 1: 95% (7.35 mmol) Step 2: 107% (7.83 mmol) Step 3: 94% (7.36 mmol) ASN_CC-10

2-Chloro-N-[6-(3,9- diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-5-(trifluoromethyl)- benzamide (ASN_CC-10) (ACI_CC-31) tert-butyl 3,9- diazaspiro[5.5] undecane-3- carboxylate Step 1: 90% (6.98 mmol) Step 2: 105% (7.31 mmol) Step 3: 95% (6.94 mmol) ASN_CC-11

2,3-Dichloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzamide (ASN_CC-11) (ACI_CC-32) tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate Step 1: 97% (9.04 mmol) Step 2: 104% (9.40 mmol) Step 3: 97% (9.11 mmol) ASN_CC-12

2,3-Dichloro-N-[6-(3,9- diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzamide (ASN_CC-12) (ACI_CC-32) tert-butyl 3,9- diazaspiro[5.5] undecane-3- carboxylate Step 1: 81% (7.60 mmol) Step 2: 99% (7.50 mmol) Step 3: 100% (7.50 mmol) ASN_CC-13

2-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-6-methyl- benzamide (ASN_CC-13) (ACI_CC-33) tert-butyl 2,8- diazaspiro[4.5]decane-8- carboxylate Step 1: 87% (8.83 mmol) Step 2: 103% (9.06 mmol) Step 3: 102% (9.23 mmol) ASN_CC-14

2-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-6-fluoro- benzamide (ASN_CC-14) (ACI_CC-34) tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate Step 1: 99% (8.13 mmol) Step 2: 101% (8.18 mmol) Step 3: 100% (8.22 mmol) ASN_CC-15

2-Chloro-N-[6-(3,9- diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-6-fluoro- benzamide (ASN_CC-15) (ACI_CC-34) tert-butyl 3,9- diazaspiro[5.5] undecane-3- carboxylate Step 1: 74% (6.07 mmol) Step 2: 113% (6.84 mmol) Step 3: 100% (6.85 mmol) ASN_CC-16

2-Chloro-N-[2-(3,8- diazaspiro[4.5]decane-3- carbonyl)-6,7,8,9-tetrahydro- 5H-benzocyclohepten-9-yl]- benzamide (ASN_CC-16) (ACI_CC-25) tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate Step 1: 89% (6.46 mmol) Step 2: 113% (7.28 mmol) Step 3: 92% (6.67 mmol) ASN_CC-17

2-Chloro-N-[[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-methyl]- benzamide (ASN_CC-17) (ACI_CC-26) tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate Step 1: 88% (7.15 mmol) Step 2: 106% (7.59 mmol) Step 3: 96% (7.30 mmol) ASN_CC-18

8-Chloro-2-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-4-methyl-3,4- dihydro-2H-pyrrolo[3,4- b]indol-1-one (ASN_CC-18) (ACI_CC-29) tert-butyl 2,8- diazaspiro[4.5]decane-8- carboxylate Step 1: 101% (6.17 mmol) Step 2: 97% (6.01 mmol) Step 3: 105% (6.30 mmol) ASN_CC-19

8-Chloro-2-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-3,4-dihydro-2H- pyrrolo[1,2-a]pyrazin-1-one (ASN_CC-19) (ACI_CC-28) tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate Step 1: 91% (1.67 mmol) Step 2: 98% (1.62 mmol) Step 3: 109% (1.76 mmol) ASN_CC-20

2-Chloro-N-[6-[2-(2,8- diazaspiro[4.5]decan-2-yl)-2- oxo-ethyl]-2,3-dihydro-1H- inden-1-yl]-benzamide (ASN_CC-20) (ACI_CC-27) tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate Step 1: 96% (7.27 mmol) Step 2: 106% (7.62 mmol) Step 3: 90% (6.84 mmol)

2) Synthesis of Acid Units, Acid Chlorides, Sulfonyl Chlorides and Isocyanates and Aldehydes (ACI_CC, ACL—CC, SCI_CC, ICN_CC, ALD_CC):

All building blocks (aldehyde, acid chloride, sulfonyl chloride and isocyanate) required for the synthesis of library no. 3 have been described and depicted under library no. 1 (→3) Synthesis of the acid units, acid chlorides, sulfonyl chlorides and isocyanates and aldehydes (ACI_CC, ACL_CC, SCI_CC, ICN_CC, ALD_CC).

3) Parallel synthesis

General:

The spiroamines amine ASN_CC were reacted in parallel fashion via Parallel Method 3 with sulfonyl chlorides SCI_CC to give the sulfonamidic products IND_CC. ASN_CC were reacted in parallel fashion via Parallel Method 4 with isocyanates ISN_CC to give the urea products IND_CC. ASN_CC were reacted in parallel fashion via Parallel Method 5 with acid chlorides ACL_CC to give the amidic products IND_CC. ASN_CC were reacted in parallel fashion via Parallel Method 6 with aldehydes ALD_CC to give the reductively aminated products IND_CC. The crude products of the parallel synthesis were purified by column chromatography. It was possible to demonstrate the identity of the products by analytical HPLC-MS measurements (cf. HPLC-MS data).

Parallel Method 3: Sulfonylation

To a solution of ASN_CC (100 μmol) in methylene chloride (1 ml) was added a mixture of the sulfonyl chloride (SCI_CC) (150 μmol) and diisopropylethylamine (300 μmol) in methylene chloride (1.5 ml). The reaction mixture was stirred at room temperature for 12 h. The reaction mixture was treated with aqueous NaOH solution (1.5 ml, 1 mol/l) and sat. NaCl solution (1.5 ml) and stirred at room temperature for 30 min. The organic phase was separated, the aqueous phase was extracted with methylene chloride for two times. The combined organic phases were concentrated under reduced pressure. The crude product was purified via a HPLCMS system.

Parallel Method 4: Urea Formation

To a solution of ASN_CC (100 μmol) in methylene chloride (1 ml) was added a mixture of the sulfonyl chloride (ICN_CC) (150 μmol) and diisopropylethylamine (300 μmol) in methylene chloride (1.5 ml). The reaction mixture was stirred at room temperature for 12 h. The reaction mixture was treated with aqueous NaOH solution (1.5 ml, 1 mol/l) and sat. NaCl solution (1.5 ml) and stirred at room temperature for 30 min. The organic phase was separated, the aqueous phase was extracted with methylene chloride for two times. The combined organic phases were concentrated under reduced pressure. The crude product was purified via a HPLCMS system.

Parallel Method 5: Amide Formation

To a solution of ASN_CC (100 μmol) in methylene chloride (1 ml) was added a mixture of the sulfonyl chloride (ACL_CC) (150 μmol) and diisopropylethylamine (300 μmol) in methylene chloride (1.5 ml). The reaction mixture was stirred at room temperature for 12 h. The reaction mixture was treated with aqueous NaOH solution (1.5 ml, 1 mol/l) and sat. NaCl solution (1.5 ml) and stirred at room temperature for 30 min. The organic phase was separated, the aqueous phase was extracted with methylene chloride for two times. The combined organic phases were concentrated under reduced pressure. The crude product was purified via a HPLCMS system.

Parallel Method 6: Reductive Amination

To a solution of ALD_CC (150 μmol) in methylene chloride (2.5 ml) were added the amine (ASN_CC) (100 μmol) in methylene chloride (1 ml) and acetic acid (12.5 μmol) in methylene chloride (0.5 ml). The reaction mixture was stirred at room temperature for 1 h. Sodium triacetoxyborohydride (250 μmol) was added and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was treated with halfsat. NaHCO₃ solution (2 ml) and sat. NaCl solution (1 ml) and stirred at room temperature for 15 min. The organic phase was separated, the aqueous phase was extracted with methylene chloride for two times. The combined organic phases were concentrated under reduced pressure. The crude product was purified via a HPLCMS system.

Synthesis Matrix:

ACI_CC, SCI_CC, Amine Example no. ICN_CC or ALD_CC (ASN_CC) Method no. IND_CC-500 SCI_CC-07 ASN_CC_04 No. 3 IND_CC-501 SCI_CC-04 ASN_CC_04 No. 3 IND_CC-502 ICN_CC-09 ASN_CC_04 No. 4 IND_CC-503 ICN_CC-03 ASN_CC_04 No. 4 IND_CC-504 ALD_CC-12 ASN_CC_04 No. 6 IND_CC-505 ALD_CC-23 ASN_CC_05 No. 6 IND_CC-506 ALD_CC-20 ASN_CC_05 No. 6 IND_CC-507 ALD_CC-29 ASN_CC_06 No. 6 IND_CC-508 ALD_CC-27 ASN_CC_06 No. 6 IND_CC-509 ALD_CC-01 ASN_CC_06 No. 6 IND_CC-510 ALD_CC-02 ASN_CC_06 No. 6 IND_CC-511 ALD_CC-07 ASN_CC_06 No. 6 IND_CC-512 ALD_CC-05 ASN_CC_06 No. 6 IND_CC-513 ALD_CC-12 ASN_CC_06 No. 6 IND_CC-514 ALD_CC-13 ASN_CC_06 No. 6 IND_CC-515 ALD_CC-14 ASN_CC_06 No. 6 IND_CC-516 ALD_CC-22 ASN_CC_06 No. 6 IND_CC-517 ALD_CC-15 ASN_CC_06 No. 6 IND_CC-518 ALD_CC-07 ASN_CC_03 No. 6 IND_CC-519 ALD_CC-05 ASN_CC_03 No. 6 IND_CC-520 ALD_CC-12 ASN_CC_03 No. 6 IND_CC-521 ALD_CC-13 ASN_CC_03 No. 6 IND_CC-522 ALD_CC-14 ASN_CC_03 No. 6 IND_CC-523 ALD_CC-22 ASN_CC_03 No. 6 IND_CC-524 ALD_CC-11 ASN_CC_03 No. 6 IND_CC-525 ALD_CC-15 ASN_CC_03 No. 6 IND_CC-526 ALD_CC-25 ASN_CC_06 No. 6 IND_CC-527 ALD_CC-28 ASN_CC_06 No. 6 IND_CC-528 ALD_CC-33 ASN_CC_06 No. 6 IND_CC-529 ALD_CC-03 ASN_CC_06 No. 6 IND_CC-530 ALD_CC-04 ASN_CC_06 No. 6 IND_CC-531 ALD_CC-31 ASN_CC_06 No. 6 IND_CC-532 ALD_CC-17 ASN_CC_06 No. 6 IND_CC-533 ALD_CC-08 ASN_CC_06 No. 6 IND_CC-534 ALD_CC-21 ASN_CC_06 No. 6 IND_CC-535 ALD_CC-23 ASN_CC_06 No. 6 IND_CC-536 ALD_CC-25 ASN_CC_03 No. 6 IND_CC-537 ALD_CC-03 ASN_CC_03 No. 6 IND_CC-538 ALD_CC-04 ASN_CC_03 No. 6 IND_CC-539 ALD_CC-08 ASN_CC_03 No. 6 IND_CC-540 ALD_CC-21 ASN_CC_03 No. 6 IND_CC-541 ALD_CC-23 ASN_CC_03 No. 6 IND_CC-542 ALD_CC-13 ASN_CC_04 No. 6 IND_CC-543 ALD_CC-14 ASN_CC_04 No. 6 IND_CC-544 ALD_CC-22 ASN_CC_04 No. 6 IND_CC-545 ALD_CC-11 ASN_CC_04 No. 6 IND_CC-546 ALD_CC-15 ASN_CC_04 No. 6 IND_CC-547 ALD_CC-14 ASN_CC_02 No. 6 IND_CC-548 ALD_CC-11 ASN_CC_02 No. 6 IND_CC-549 ALD_CC-13 ASN_CC_05 No. 6 IND_CC-550 ALD_CC-14 ASN_CC_05 No. 6 IND_CC-551 ALD_CC-22 ASN_CC_05 No. 6 IND_CC-552 ALD_CC-11 ASN_CC_05 No. 6 IND_CC-553 ALD_CC-28 ASN_CC_04 No. 6 IND_CC-554 ALD_CC-33 ASN_CC_04 No. 6 IND_CC-555 ALD_CC-18 ASN_CC_04 No. 6 IND_CC-556 ALD_CC-03 ASN_CC_04 No. 6 IND_CC-557 ALD_CC-04 ASN_CC_04 No. 6 IND_CC-558 ALD_CC-04 ASN_CC_05 No. 6 IND_CC-559 ALD_CC-31 ASN_CC_04 No. 6 IND_CC-560 ALD_CC-17 ASN_CC_04 No. 6 IND_CC-561 ALD_CC-08 ASN_CC_04 No. 6 IND_CC-562 ALD_CC-21 ASN_CC_04 No. 6 IND_CC-563 ALD_CC-23 ASN_CC_04 No. 6 IND_CC-564 ALD_CC-16 ASN_CC_04 No. 6 IND_CC-565 ALD_CC-32 ASN_CC_04 No. 6 IND_CC-566 ALD_CC-30 ASN_CC_04 No. 6 IND_CC-567 ALD_CC-19 ASN_CC_04 No. 6 IND_CC-568 ALD_CC-20 ASN_CC_04 No. 6 IND_CC-569 ALD_CC-08 ASN_CC_02 No. 6 IND_CC-570 ALD_CC-19 ASN_CC_02 No. 6 IND_CC-571 ALD_CC-20 ASN_CC_02 No. 6 IND_CC-572 ALD_CC-21 ASN_CC_05 No. 6 IND_CC-573 ACL_CC-15 ASN_CC_04 No. 5 IND_CC-574 ACL_CC-18 ASN_CC_04 No. 5 IND_CC-575 ACL_CC-28 ASN_CC_04 No. 5 IND_CC-576 ACL_CC-07 ASN_CC_04 No. 5 IND_CC-577 ACL_CC-24 ASN_CC_04 No. 5 IND_CC-578 ACL_CC-22 ASN_CC_04 No. 5 IND_CC-579 ACL_CC-21 ASN_CC_04 No. 5 IND_CC-580 ACL_CC-22 ASN_CC_01 No. 5 IND_CC-581 ACL_CC-21 ASN_CC_01 No. 5 IND_CC-582 ACL_CC-15 ASN_CC_02 No. 5 IND_CC-583 ACL_CC-18 ASN_CC_02 No. 5 IND_CC-584 ACL_CC-28 ASN_CC_02 No. 5 IND_CC-585 ACL_CC-07 ASN_CC_02 No. 5 IND_CC-586 ACL_CC-24 ASN_CC_02 No. 5 IND_CC-587 ACL_CC-22 ASN_CC_02 No. 5 IND_CC-588 ACL_CC-21 ASN_CC_02 No. 5 IND_CC-589 ACL_CC-15 ASN_CC_05 No. 5 IND_CC-590 ACL_CC-18 ASN_CC_05 No. 5 IND_CC-591 ACL_CC-28 ASN_CC_05 No. 5 IND_CC-592 ACL_CC-24 ASN_CC_05 No. 5 IND_CC-593 ACL_CC-22 ASN_CC_05 No. 5 IND_CC-594 ACL_CC-38 ASN_CC_06 No. 5 IND_CC-595 ACL_CC-20 ASN_CC_06 No. 5 IND_CC-596 ACL_CC-05 ASN_CC_06 No. 5 IND_CC-597 ACL_CC-15 ASN_CC_06 No. 5 IND_CC-598 ACL_CC-18 ASN_CC_06 No. 5 IND_CC-599 ACL_CC-28 ASN_CC_06 No. 5 IND_CC-600 ACL_CC-07 ASN_CC_06 No. 5 IND_CC-601 ACL_CC-22 ASN_CC_06 No. 5 IND_CC-602 ACL_CC-21 ASN_CC_06 No. 5 IND_CC-603 ACL_CC-15 ASN_CC_03 No. 5 IND_CC-604 ACL_CC-18 ASN_CC_03 No. 5 IND_CC-605 ACL_CC-28 ASN_CC_03 No. 5 IND_CC-606 ACL_CC-07 ASN_CC_03 No. 5 IND_CC-607 ACL_CC-22 ASN_CC_03 No. 5 IND_CC-608 SCI_CC-08 ASN_CC_06 No. 3 IND_CC-609 SCI_CC-07 ASN_CC_06 No. 3 IND_CC-610 SCI_CC-16 ASN_CC_06 No. 3 IND_CC-611 SCI_CC-04 ASN_CC_06 No. 3 IND_CC-612 SCI_CC-22 ASN_CC_06 No. 3 IND_CC-613 SCI_CC-03 ASN_CC_06 No. 3 IND_CC-614 SCI_CC-23 ASN_CC_06 No. 3 IND_CC-615 SCI_CC-08 ASN_CC_03 No. 3 IND_CC-616 SCI_CC-07 ASN_CC_03 No. 3 IND_CC-617 SCI_CC-16 ASN_CC_03 No. 3 IND_CC-618 SCI_CC-04 ASN_CC_03 No. 3 IND_CC-619 SCI_CC-23 ASN_CC_03 No. 3 IND_CC-620 ALD_CC-29 ASN_CC_07 No. 6 IND_CC-621 ALD_CC-13 ASN_CC_07 No. 6 IND_CC-622 ALD_CC-22 ASN_CC_07 No. 6 IND_CC-623 ALD_CC-11 ASN_CC_07 No. 6 IND_CC-624 ALD_CC-29 ASN_CC_08 No. 6 IND_CC-625 ALD_CC-27 ASN_CC_08 No. 6 IND_CC-626 ALD_CC-01 ASN_CC_08 No. 6 IND_CC-627 ALD_CC-02 ASN_CC_08 No. 6 IND_CC-628 ALD_CC-13 ASN_CC_08 No. 6 IND_CC-629 ALD_CC-22 ASN_CC_08 No. 6 IND_CC-630 ALD_CC-11 ASN_CC_08 No. 6 IND_CC-631 ALD_CC-27 ASN_CC_09 No. 6 IND_CC-632 ALD_CC-12 ASN_CC_09 No. 6 IND_CC-633 ALD_CC-13 ASN_CC_09 No. 6 IND_CC-634 ALD_CC-14 ASN_CC_09 No. 6 IND_CC-635 ALD_CC-22 ASN_CC_09 No. 6 IND_CC-636 ALD_CC-11 ASN_CC_09 No. 6 IND_CC-637 ALD_CC-15 ASN_CC_09 No. 6 IND_CC-638 ALD_CC-29 ASN_CC_10 No. 6 IND_CC-639 ALD_CC-27 ASN_CC_10 No. 6 IND_CC-640 ALD_CC-01 ASN_CC_10 No. 6 IND_CC-641 ALD_CC-02 ASN_CC_10 No. 6 IND_CC-642 ALD_CC-07 ASN_CC_10 No. 6 IND_CC-643 ALD_CC-05 ASN_CC_10 No. 6 IND_CC-644 ALD_CC-12 ASN_CC_10 No. 6 IND_CC-645 ALD_CC-13 ASN_CC_10 No. 6 IND_CC-646 ALD_CC-14 ASN_CC_10 No. 6 IND_CC-647 ALD_CC-22 ASN_CC_10 No. 6 IND_CC-648 ALD_CC-11 ASN_CC_10 No. 6 IND_CC-649 ALD_CC-15 ASN_CC_10 No. 6 IND_CC-650 ALD_CC-08 ASN_CC_07 No. 6 IND_CC-651 ALD_CC-21 ASN_CC_07 No. 6 IND_CC-652 ALD_CC-18 ASN_CC_08 No. 6 IND_CC-653 ALD_CC-08 ASN_CC_08 No. 6 IND_CC-654 ALD_CC-21 ASN_CC_08 No. 6 IND_CC-655 ALD_CC-28 ASN_CC_09 No. 6 IND_CC-656 ALD_CC-18 ASN_CC_09 No. 6 IND_CC-657 ALD_CC-17 ASN_CC_09 No. 6 IND_CC-658 ALD_CC-08 ASN_CC_09 No. 6 IND_CC-659 ALD_CC-21 ASN_CC_09 No. 6 IND_CC-660 ALD_CC-23 ASN_CC_09 No. 6 IND_CC-661 ALD_CC-28 ASN_CC_10 No. 6 IND_CC-662 ALD_CC-33 ASN_CC_10 No. 6 IND_CC-663 ALD_CC-18 ASN_CC_10 No. 6 IND_CC-664 ALD_CC-31 ASN_CC_10 No. 6 IND_CC-665 ALD_CC-17 ASN_CC_10 No. 6 IND_CC-666 ALD_CC-08 ASN_CC_10 No. 6 IND_CC-667 ALD_CC-21 ASN_CC_10 No. 6 IND_CC-668 ALD_CC-23 ASN_CC_10 No. 6 IND_CC-669 ALD_CC-03 ASN_CC_10 No. 6 IND_CC-670 ALD_CC-04 ASN_CC_10 No. 6 IND_CC-671 ALD_CC-19 ASN_CC_07 No. 6 IND_CC-672 ALD_CC-20 ASN_CC_07 No. 6 IND_CC-673 ALD_CC-24 ASN_CC_07 No. 6 IND_CC-674 ALD_CC-34 ASN_CC_07 No. 6 IND_CC-675 ALD_CC-35 ASN_CC_07 No. 6 IND_CC-676 ALD_CC-30 ASN_CC_08 No. 6 IND_CC-677 ALD_CC-19 ASN_CC_08 No. 6 IND_CC-678 ALD_CC-20 ASN_CC_08 No. 6 IND_CC-679 ALD_CC-24 ASN_CC_08 No. 6 IND_CC-680 ALD_CC-26 ASN_CC_08 No. 6 IND_CC-681 ALD_CC-10 ASN_CC_08 No. 6 IND_CC-682 ALD_CC-16 ASN_CC_09 No. 6 IND_CC-683 ALD_CC-30 ASN_CC_09 No. 6 IND_CC-684 ALD_CC-19 ASN_CC_09 No. 6 IND_CC-685 ALD_CC-20 ASN_CC_09 No. 6 IND_CC-686 ALD_CC-24 ASN_CC_09 No. 6 IND_CC-687 ALD_CC-26 ASN_CC_09 No. 6 IND_CC-688 ALD_CC-09 ASN_CC_09 No. 6 IND_CC-689 ALD_CC-06 ASN_CC_09 No. 6 IND_CC-690 ALD_CC-10 ASN_CC_09 No. 6 IND_CC-691 ALD_CC-34 ASN_CC_09 No. 6 IND_CC-692 ALD_CC-35 ASN_CC_09 No. 6 IND_CC-693 ALD_CC-32 ASN_CC_10 No. 6 IND_CC-694 ALD_CC-30 ASN_CC_10 No. 6 IND_CC-695 ALD_CC-19 ASN_CC_10 No. 6 IND_CC-696 ALD_CC-20 ASN_CC_10 No. 6 IND_CC-697 ALD_CC-24 ASN_CC_10 No. 6 IND_CC-698 ALD_CC-26 ASN_CC_10 No. 6 IND_CC-699 ALD_CC-09 ASN_CC_10 No. 6 IND_CC-700 ALD_CC-06 ASN_CC_10 No. 6 IND_CC-701 ALD_CC-10 ASN_CC_10 No. 6 IND_CC-702 ALD_CC-34 ASN_CC_10 No. 6 IND_CC-703 ALD_CC-35 ASN_CC_10 No. 6 IND_CC-704 ICN_CC-10 ASN_CC_06 No. 4 IND_CC-705 ICN_CC-03 ASN_CC_06 No. 4 IND_CC-706 ICN_CC-12 ASN_CC_06 No. 4 IND_CC-707 ICN_CC-04 ASN_CC_06 No. 4 IND_CC-708 ICN_CC-11 ASN_CC_06 No. 4 IND_CC-709 ICN_CC-06 ASN_CC_06 No. 4 IND_CC-710 ICN_CC-07 ASN_CC_06 No. 4 IND_CC-711 ICN_CC-05 ASN_CC_06 No. 4 IND_CC-712 ICN_CC-10 ASN_CC_03 No. 4 IND_CC-713 ICN_CC-09 ASN_CC_03 No. 4 IND_CC-714 ICN_CC-08 ASN_CC_03 No. 4 IND_CC-715 ICN_CC-03 ASN_CC_03 No. 4 IND_CC-716 ICN_CC-12 ASN_CC_03 No. 4 IND_CC-717 ICN_CC-11 ASN_CC_03 No. 4 IND_CC-718 ICN_CC-06 ASN_CC_03 No. 4 IND_CC-719 ICN_CC-05 ASN_CC_03 No. 4 IND_CC-720 ICN_CC-14 ASN_CC_03 No. 4 IND_CC-721 ICN_CC-13 ASN_CC_03 No. 4 IND_CC-722 ALD_CC-31 ASN_CC_11 No. 6 IND_CC-723 ALD_CC-17 ASN_CC_11 No. 6 IND_CC-724 ALD_CC-23 ASN_CC_11 No. 6 IND_CC-725 ALD_CC-04 ASN_CC_11 No. 6 IND_CC-726 ALD_CC-03 ASN_CC_12 No. 6 IND_CC-727 ALD_CC-04 ASN_CC_12 No. 6 IND_CC-728 ALD_CC-33 ASN_CC_13 No. 6 IND_CC-729 ALD_CC-31 ASN_CC_13 No. 6 IND_CC-730 ALD_CC-17 ASN_CC_13 No. 6 IND_CC-731 ALD_CC-08 ASN_CC_13 No. 6 IND_CC-732 ALD_CC-21 ASN_CC_13 No. 6 IND_CC-733 ALD_CC-23 ASN_CC_13 No. 6 IND_CC-734 ALD_CC-03 ASN_CC_13 No. 6 IND_CC-735 ALD_CC-04 ASN_CC_13 No. 6 IND_CC-736 ALD_CC-33 ASN_CC_14 No. 6 IND_CC-737 ALD_CC-31 ASN_CC_14 No. 6 IND_CC-738 ALD_CC-17 ASN_CC_14 No. 6 IND_CC-739 ALD_CC-08 ASN_CC_14 No. 6 IND_CC-740 ALD_CC-23 ASN_CC_14 No. 6 IND_CC-741 ALD_CC-03 ASN_CC_14 No. 6 IND_CC-742 ALD_CC-32 ASN_CC_11 No. 6 IND_CC-743 ALD_CC-30 ASN_CC_11 No. 6 IND_CC-744 ALD_CC-19 ASN_CC_11 No. 6 IND_CC-745 ALD_CC-20 ASN_CC_11 No. 6 IND_CC-746 ALD_CC-24 ASN_CC_11 No. 6 IND_CC-747 ALD_CC-26 ASN_CC_11 No. 6 IND_CC-748 ALD_CC-09 ASN_CC_11 No. 6 IND_CC-749 ALD_CC-10 ASN_CC_11 No. 6 IND_CC-750 ALD_CC-34 ASN_CC_11 No. 6 IND_CC-751 ALD_CC-35 ASN_CC_11 No. 6 IND_CC-752 ALD_CC-32 ASN_CC_12 No. 6 IND_CC-753 ALD_CC-30 ASN_CC_12 No. 6 IND_CC-754 ALD_CC-19 ASN_CC_12 No. 6 IND_CC-755 ALD_CC-20 ASN_CC_12 No. 6 IND_CC-756 ALD_CC-24 ASN_CC_12 No. 6 IND_CC-757 ALD_CC-26 ASN_CC_12 No. 6 IND_CC-758 ALD_CC-10 ASN_CC_12 No. 6 IND_CC-759 ALD_CC-34 ASN_CC_12 No. 6 IND_CC-760 ALD_CC-35 ASN_CC_12 No. 6 IND_CC-761 ALD_CC-16 ASN_CC_13 No. 6 IND_CC-762 ALD_CC-32 ASN_CC_13 No. 6 IND_CC-763 ALD_CC-30 ASN_CC_13 No. 6 IND_CC-764 ALD_CC-19 ASN_CC_13 No. 6 IND_CC-765 ALD_CC-20 ASN_CC_13 No. 6 IND_CC-766 ALD_CC-24 ASN_CC_13 No. 6 IND_CC-767 ALD_CC-26 ASN_CC_13 No. 6 IND_CC-768 ALD_CC-09 ASN_CC_13 No. 6 IND_CC-769 ALD_CC-10 ASN_CC_13 No. 6 IND_CC-770 ALD_CC-34 ASN_CC_13 No. 6 IND_CC-771 ALD_CC-35 ASN_CC_13 No. 6 IND_CC-772 ALD_CC-32 ASN_CC_14 No. 6 IND_CC-773 ALD_CC-30 ASN_CC_14 No. 6 IND_CC-774 ALD_CC-19 ASN_CC_14 No. 6 IND_CC-775 ALD_CC-20 ASN_CC_14 No. 6 IND_CC-776 ALD_CC-24 ASN_CC_14 No. 6 IND_CC-777 ALD_CC-26 ASN_CC_14 No. 6 IND_CC-778 ALD_CC-09 ASN_CC_14 No. 6 IND_CC-779 ALD_CC-06 ASN_CC_14 No. 6 IND_CC-780 ALD_CC-10 ASN_CC_14 No. 6 IND_CC-781 ALD_CC-34 ASN_CC_14 No. 6 IND_CC-782 ALD_CC-35 ASN_CC_14 No. 6 IND_CC-783 ALD_CC-29 ASN_CC_15 No. 6 IND_CC-784 ALD_CC-01 ASN_CC_15 No. 6 IND_CC-785 ALD_CC-02 ASN_CC_15 No. 6 IND_CC-786 ALD_CC-07 ASN_CC_15 No. 6 IND_CC-787 ALD_CC-05 ASN_CC_15 No. 6 IND_CC-788 ALD_CC-12 ASN_CC_15 No. 6 IND_CC-789 ALD_CC-13 ASN_CC_15 No. 6 IND_CC-790 ALD_CC-14 ASN_CC_15 No. 6 IND_CC-791 ALD_CC-22 ASN_CC_15 No. 6 IND_CC-792 ALD_CC-11 ASN_CC_15 No. 6 IND_CC-793 ALD_CC-15 ASN_CC_15 No. 6 IND_CC-794 ALD_CC-11 ASN_CC_18 No. 6 IND_CC-795 ALD_CC-15 ASN_CC_18 No. 6 IND_CC-796 ALD_CC-25 ASN_CC_15 No. 6 IND_CC-797 ALD_CC-18 ASN_CC_15 No. 6 IND_CC-798 ALD_CC-31 ASN_CC_15 No. 6 IND_CC-799 ALD_CC-17 ASN_CC_15 No. 6 IND_CC-800 ALD_CC-21 ASN_CC_15 No. 6 IND_CC-801 ALD_CC-23 ASN_CC_15 No. 6 IND_CC-802 ALD_CC-03 ASN_CC_15 No. 6 IND_CC-803 ALD_CC-04 ASN_CC_15 No. 6 IND_CC-804 ALD_CC-19 ASN_CC_20 No. 6 IND_CC-805 ALD_CC-20 ASN_CC_20 No. 6 IND_CC-806 ALD_CC-09 ASN_CC_20 No. 6 IND_CC-807 ALD_CC-06 ASN_CC_20 No. 6

Analytical Data:

Example no. [M+] found R.t. [min] IND_CC-500 614.3 0.74 IND_CC-501 603.3 0.71 IND_CC-502 609.4 0.74 IND_CC-503 582.3 0.68 IND_CC-504 564.3 0.51 IND_CC-505 567.4 0.53 IND_CC-506 594.4 0.51 IND_CC-507 531.4 0.50 IND_CC-508 532.4 0.41 IND_CC-509 543.4 0.49 IND_CC-510 543.4 0.44 IND_CC-511 543.4 0.46 IND_CC-512 545.4 0.52 IND_CC-513 578.4 0.52 IND_CC-514 578.4 0.54 IND_CC-515 578.3 0.53 IND_CC-516 578.3 0.53 IND_CC-517 590.4 0.54 IND_CC-518 569.4 0.52 IND_CC-519 571.4 0.57 IND_CC-520 604.4 0.57 IND_CC-521 604.4 0.59 IND_CC-522 604.4 0.57 IND_CC-523 604.4 0.58 IND_CC-524 616.4 0.59 IND_CC-525 616.4 0.59 IND_CC-526 546.4 0.38 IND_CC-527 546.4 0.39 IND_CC-528 546.4 0.38 IND_CC-529 594.3 0.54 IND_CC-530 594.3 0.53 IND_CC-531 560.4 0.48 IND_CC-532 561.4 0.49 IND_CC-533 567.3 0.52 IND_CC-534 567.4 0.51 IND_CC-535 567.4 0.51 IND_CC-536 572.4 0.45 IND_CC-537 620.4 0.59 IND_CC-538 620.4 0.58 IND_CC-539 593.4 0.56 IND_CC-540 593.4 0.56 IND_CC-541 593.4 0.56 IND_CC-542 564.4 0.53 IND_CC-543 564.3 0.51 IND_CC-544 564.3 0.51 IND_CC-545 576.4 0.52 IND_CC-546 576.4 0.53 IND_CC-547 570.3 0.53 IND_CC-548 582.3 0.54 IND_CC-549 578.4 0.55 IND_CC-550 578.4 0.54 IND_CC-551 578.4 0.54 IND_CC-552 590.4 0.54 IND_CC-553 532.4 0.39 IND_CC-554 532.4 0.37 IND_CC-555 536.3 0.46 IND_CC-556 580.3 0.59 IND_CC-557 580.3 0.52 IND_CC-558 594.3 0.54 IND_CC-559 546.4 0.46 IND_CC-560 547.3 0.47 IND_CC-561 553.3 0.49 IND_CC-562 553.3 0.49 IND_CC-563 553.3 0.50 IND_CC-564 560.4 0.47 IND_CC-565 560.4 0.48 IND_CC-566 573.4 0.49 IND_CC-567 579.3 0.47 IND_CC-568 580.4 0.47 IND_CC-569 559.3 0.52 IND_CC-570 585.3 0.49 IND_CC-571 586.3 0.50 IND_CC-572 567.4 0.52 IND_CC-573 506.3 0.68 IND_CC-574 536.4 0.72 IND_CC-575 594.3 0.72 IND_CC-576 578.3 0.70 IND_CC-577 590.3 0.74 IND_CC-578 602.4 0.73 IND_CC-579 602.4 0.73 IND_CC-580 626.5 0.74 IND_CC-581 626.5 0.74 IND_CC-582 512.3 0.68 IND_CC-583 542.3 0.75 IND_CC-584 600.2 0.75 IND_CC-585 584.3 0.73 IND_CC-586 596.3 0.77 IND_CC-587 608.4 0.76 IND_CC-588 608.4 0.76 IND_CC-589 520.3 0.69 IND_CC-590 550.4 0.75 IND_CC-591 608.3 0.75 IND_CC-592 604.4 0.77 IND_CC-593 616.4 0.76 IND_CC-594 558.4 0.63 IND_CC-595 603.4 0.70 IND_CC-596 581.3 0.69 IND_CC-597 520.4 0.67 IND_CC-598 550.4 0.74 IND_CC-599 608.3 0.74 IND_CC-600 592.3 0.73 IND_CC-601 616.4 0.75 IND_CC-602 616.4 0.75 IND_CC-603 546.3 0.72 IND_CC-604 576.4 0.78 IND_CC-605 634.3 0.79 IND_CC-606 618.4 0.77 IND_CC-607 642.4 0.80 IND_CC-608 632.2 0.80 IND_CC-609 628.3 0.77 IND_CC-610 635.3 0.76 IND_CC-611 617.3 0.74 IND_CC-612 645.4 0.76 IND_CC-613 558.3 0.71 IND_CC-614 645.4 0.76 IND_CC-615 658.3 0.84 IND_CC-616 654.3 0.81 IND_CC-617 661.3 0.80 IND_CC-618 643.3 0.78 IND_CC-619 671.4 0.80 IND_CC-620 535.4 0.52 IND_CC-621 582.3 0.57 IND_CC-622 582.3 0.57 IND_CC-623 594.4 0.57 IND_CC-624 549.3 0.54 IND_CC-625 550.3 0.45 IND_CC-626 561.4 0.53 IND_CC-627 561.4 0.49 IND_CC-628 596.4 0.58 IND_CC-629 596.3 0.57 IND_CC-630 608.4 0.58 IND_CC-631 586.3 0.48 IND_CC-632 632.3 0.57 IND_CC-633 632.3 0.60 IND_CC-634 632.3 0.59 IND_CC-635 632.3 0.60 IND_CC-636 644.4 0.59 IND_CC-637 644.4 0.60 IND_CC-638 599.4 0.57 IND_CC-639 600.4 0.48 IND_CC-640 611.4 0.56 IND_CC-641 611.4 0.52 IND_CC-642 611.4 0.53 IND_CC-643 613.4 0.58 IND_CC-644 646.4 0.59 IND_CC-645 646.4 0.60 IND_CC-646 646.4 0.59 IND_CC-647 646.4 0.59 IND_CC-648 658.4 0.60 IND_CC-649 658.4 0.61 IND_CC-650 571.3 0.55 IND_CC-651 571.3 0.55 IND_CC-652 568.3 0.53 IND_CC-653 585.3 0.55 IND_CC-654 585.3 0.56 IND_CC-655 600.4 0.46 IND_CC-656 604.3 0.54 IND_CC-657 615.3 0.55 IND_CC-658 621.4 0.56 IND_CC-659 621.4 0.57 IND_CC-660 621.3 0.58 IND_CC-661 614.4 0.48 IND_CC-662 614.2 0.46 IND_CC-663 618.3 0.56 IND_CC-664 628.3 0.56 IND_CC-665 629.3 0.57 IND_CC-666 635.3 0.58 IND_CC-667 635.3 0.59 IND_CC-668 635.3 0.59 IND_CC-669 662.3 0.62 IND_CC-670 662.3 0.60 IND_CC-671 597.3 0.52 IND_CC-672 598.3 0.53 IND_CC-673 601.3 0.54 IND_CC-674 529.3 0.61 IND_CC-675 592.3 0.61 IND_CC-676 605.3 0.56 IND_CC-677 611.3 0.53 IND_CC-678 612.3 0.55 IND_CC-679 615.3 0.55 IND_CC-680 526.3 0.56 IND_CC-681 574.3 0.60 IND_CC-682 628.3 0.55 IND_CC-683 641.4 0.57 IND_CC-684 647.3 0.55 IND_CC-685 648.3 0.56 IND_CC-686 651.3 0.55 IND_CC-687 562.3 0.56 IND_CC-688 590.3 0.60 IND_CC-689 602.4 0.62 IND_CC-690 610.3 0.60 IND_CC-691 642.3 0.61 IND_CC-692 642.3 0.61 IND_CC-693 642.4 0.56 IND_CC-694 655.4 0.57 IND_CC-695 661.4 0.55 IND_CC-696 662.4 0.56 IND_CC-697 656.4 0.56 IND_CC-698 576.3 0.57 IND_CC-699 604.4 0.61 IND_CC-700 616.4 0.63 IND_CC-701 624.4 0.61 IND_CC-702 656.4 0.63 IND_CC-703 656.4 0.63 IND_CC-704 537.3 0.67 IND_CC-705 596.3 0.71 IND_CC-706 585.3 0.71 IND_CC-707 614.4 0.55 IND_CC-708 577.4 0.73 IND_CC-709 639.2 0.73 IND_CC-710 639.2 0.80 IND_CC-711 607.3 0.72 IND_CC-712 563.3 0.72 IND_CC-713 649.3 0.81 IND_CC-714 699.3 0.83 IND_CC-715 622.3 0.75 IND_CC-716 611.4 0.76 IND_CC-717 603.4 0.78 IND_CC-718 665.3 0.78 IND_CC-719 633.3 0.77 IND_CC-720 633.4 0.80 IND_CC-721 679.3 0.82 IND_CC-722 580.3 0.52 IND_CC-723 581.2 0.54 IND_CC-724 587.3 0.56 IND_CC-725 614.3 0.58 IND_CC-726 628.3 0.60 IND_CC-727 628.3 0.59 IND_CC-728 546.3 0.41 IND_CC-729 560.4 0.50 IND_CC-730 561.3 0.52 IND_CC-731 567.3 0.53 IND_CC-732 567.3 0.54 IND_CC-733 567.3 0.54 IND_CC-734 594.3 0.57 IND_CC-735 594.3 0.56 IND_CC-736 550.2 0.40 IND_CC-737 564.3 0.49 IND_CC-738 565.3 0.50 IND_CC-739 571.3 0.52 IND_CC-740 571.3 0.54 IND_CC-741 577.3 0.57 IND_CC-742 594.3 0.53 IND_CC-743 607.3 0.54 IND_CC-744 613.3 0.51 IND_CC-745 614.3 0.53 IND_CC-746 617.3 0.53 IND_CC-747 528.3 0.54 IND_CC-748 556.3 0.59 IND_CC-749 576.3 0.58 IND_CC-750 608.3 0.60 IND_CC-751 608.3 0.60 IND_CC-752 608.3 0.54 IND_CC-753 621.3 0.56 IND_CC-754 627.3 0.52 IND_CC-755 628.3 0.54 IND_CC-756 631.4 0.54 IND_CC-757 542.3 0.55 IND_CC-758 590.3 0.59 IND_CC-759 622.3 0.61 IND_CC-760 622.3 0.61 IND_CC-761 574.3 0.51 IND_CC-762 574.4 0.52 IND_CC-763 587.3 0.53 IND_CC-764 593.4 0.50 IND_CC-765 594.4 0.51 IND_CC-766 597.4 0.52 IND_CC-767 508.3 0.52 IND_CC-768 536.4 0.57 IND_CC-769 556.4 0.57 IND_CC-770 588.4 0.59 IND_CC-771 588.4 0.59 IND_CC-772 578.4 0.51 IND_CC-773 591.4 0.51 IND_CC-774 597.4 0.48 IND_CC-775 598.3 0.50 IND_CC-776 601.3 0.51 IND_CC-777 512.3 0.51 IND_CC-778 540.3 0.56 IND_CC-779 552.4 0.57 IND_CC-780 560.3 0.56 IND_CC-781 592.4 0.58 IND_CC-782 592.3 0.58 IND_CC-783 549.3 0.52 IND_CC-784 561.3 0.51 IND_CC-785 561.3 0.46 IND_CC-786 561.3 0.47 IND_CC-787 563.2 0.52 IND_CC-788 596.2 0.53 IND_CC-789 596.2 0.55 IND_CC-790 596.2 0.54 IND_CC-791 596.2 0.54 IND_CC-792 608.2 0.55 IND_CC-793 608.2 0.56 IND_CC-794 641.2 0.57 IND_CC-795 641.2 0.58 IND_CC-796 564.2 0.38 IND_CC-797 568.2 0.48 IND_CC-798 578.2 0.48 IND_CC-799 579.2 0.49 IND_CC-800 585.2 0.51 IND_CC-801 585.2 0.52 IND_CC-802 612.1 0.55 IND_CC-803 612.1 0.55 IND_CC-804 593.2 0.48 IND_CC-805 594.2 0.50 IND_CC-806 536.2 0.56 IND_CC-807 548.2 0.58

Pharmacological Data

The pharmacological data were determined as described above. The following data are given in the table below by way of example:

% % Inhibition Inhibition Example (rat B1R) at (human no. 10 μM B1R) at 10 μM H-01 97 100 H-02 100 100 H-03 104 98 H-04 106 100 H-05 105 100 H-06 98 60 H-07 69 34 H-08 100 71 H-09 102 100 H-10 103 49 H-11 103 99 H-12 102 97 H-13 101 100 H-14 101 91 H-15 11 59 H-16 102 100 H-17 102 98 H-18 104 96 H-19 102 99 H-20 105 100 H-21 105 100 H-26 101 46 H-27 102 100 H-28 102 57 H-29 55 33 H-47 101 99 H-48 97 63 H-49 100 99 H-50 98 98 H-51 96 98 Ind_CC-001 98 99 Ind_CC-002 85 97 Ind_CC-003 101 99 Ind_CC-004 98 99 Ind_CC-005 98 97 Ind_CC-006 98 98 Ind_CC-007 102 99 Ind_CC-008 74 72 Ind_CC-009 99 87 Ind_CC-010 100 97 Ind_CC-011 76 36 Ind_CC-012 100 100 Ind_CC-013 71 68 Ind_CC-014 101 93 Ind_CC-015 101 100 Ind_CC-016 102 100 Ind_CC-017 102 99 Ind_CC-018 98 98 Ind_CC-019 95 99 Ind_CC-020 88 89 Ind_CC-021 96 94 Ind_CC-022 75 91 Ind_CC-023 93 98 Ind_CC-042 101 98 Ind_CC-043 88 79 Ind_CC-044 100 97 Ind_CC-045 101 100 Ind_CC-046 68 98 Ind_CC-047 60 94 Ind_CC-048 88 98 Ind_CC-049 101 99 Ind_CC-050 93 100 Ind_CC-051 99 71 Ind_CC-052 81 62 Ind_CC-053 103 99 Ind_CC-054 102 96 Ind_CC-055 102 99 Ind_CC-056 94 41 Ind_CC-057 80 35 Ind_CC-058 101 100 Ind_CC-059 102 100 Ind_CC-060 94 93 Ind_CC-061 103 100 Ind_CC-062 104 Ind_CC-064 101 95 Ind_CC-065 98 94 Ind_CC-066 98 82 Ind_CC-067 101 94 Ind_CC-081 101 99 Ind_CC-082 101 100 Ind_CC-083 85 90 Ind_CC-084 100 99 Ind_CC-085 77 91 Ind_CC-086 99 100 Ind_CC-087 100 Ind_CC-088 93 Ind_CC-089 100 Ind_CC-090 100 42 Ind_CC-091 50 24 Ind_CC-092 101 78 Ind_CC-093 74 34 Ind_CC-094 65 42 Ind_CC-095 99 99 Ind_CC-096 101 91 Ind_CC-097 90 33 Ind_CC-098 98 34 Ind_CC-099 103 39 Ind_CC-100 104 100 Ind_CC-101 102 100 Ind_CC-102 100 87 Ind_CC-103 62 93 Ind_CC-104 102 33 Ind_CC-105 86 61 Ind_CC-106 100 100 Ind_CC-107 100 78 Ind_CC-108 51 23 Ind_CC-109 29 33 Ind_CC-110 79 52 Ind_CC-111 101 100 Ind_CC-112 104 100 Ind_CC-113 100 98 Ind_CC-114 101 99 Ind_CC-115 64 22 Ind_CC-116 77 68 Ind_CC-117 77 56 Ind_CC-118 103 100 Ind_CC-119 104 99 Ind_CC-120 99 56 Ind_CC-121 103 46 H-52 46 28 H-53 104 100 H-54 102 98 H-55 87 42 H-56 68 94 H-57 105 99 H-58 106 99 H-59 105 99 H-60 101 82 H-61 104 100 H-62 102 30 H-63 104 100 H-64 105 100 H-65 105 100 H-66 102 99 H-67 102 100 H-68 93 96 H-69 102 98 H-70 103 90 H-71 103 100 H-72 104 100 H-73 103 100 H-74 100 94 H-75 64 29 H-76 102 100 H-77 104 96 H-78 104 100 H-79 104 100 H-80 105 57 H-81 103 78 H-82 104 100 H-83 105 100 H-84 104 100 H-85 103 100 H-86 79 95 H-87 103 99 H-88 104 100 H-89 103 99 H-90 103 100 H-91 104 100 H-92 104 96 H-93 103 100 H-94 98 100 H-95 98 100 H-96 104 100 H-97 90 6 H-98 108 100 H-99 105 100 H-100 108 100 H-101 107 97 H-102 109 100 H-103 106 99 H-104 109 101 H-105 107 100 H-106 105 100 H-107 108 72 H-108 111 100 H-109 109 100 H-110 108 101 H-111 102 100 H-112 102 100 H-113 92 99 H-114 102 100 H-115 101 100 H-116 101 100 H-117 101 100 H-118 101 100 H-119 100 100 H-120 104 65 H-128 36 38 H-129 102 100 H-130 99 94 H-131 102 74 H-132 102 100 H-133 100 65 H-134 103 99 H-135 101 80 H-136 101 99 H-137 103 99 H-138 102 100 H-139 98 31 H-140 100 70 H-141 101 99 H-142 103 98 H-143 105 100 H-144 104 99 H-145 101 100 H-146 102 100 H-147 104 100 H-148 101 100 H-149 103 100 H-150 100 97 H-151 103 99 H-152 101 99 H-153 105 99 H-154 105 99 H-155 100 87 H-156 75 24 H-157 98 100 H-158 100 92 H-159 103 98 H-160 105 98 H-161 104 89 H-162 61 13 H-163 105 63 H-164 77 25 H-165 44 44 H-166 −4 21 H-167 81 35 H-168 55 96 H-169 12 54 H-170 47 56 H-171 104 100 H-172 105 99 H-173 89 100 IND_CC-200 102 100 IND_CC-201 99 IND_CC-202 103 86 IND_CC-203 103 99 IND_CC-204 102 99 IND_CC-205 103 100 IND_CC-206 103 100 IND_CC-207 101 98 IND_CC-208 100 99 IND_CC-209 102 20 IND_CC-210 104 97 IND_CC-211 104 IND_CC-212 102 58 IND_CC-213 73 IND_CC-214 102 83 IND_CC-215 103 48 IND_CC-216 103 58 IND_CC-217 95 99 IND_CC-218 103 94 IND_CC-219 104 53 IND_CC-220 104 100 IND_CC-221 104 100 IND_CC-222 60 IND_CC-223 105 97 IND_CC-224 103 100 IND_CC-225 103 71 IND_CC-226 101 98 IND_CC-227 97 IND_CC-228 104 100 IND_CC-229 102 100 IND_CC-230 104 IND_CC-231 102 100 IND_CC-232 101 96 IND_CC-233 98 86 IND_CC-234 99 85 IND_CC-235 89 IND_CC-236 96 98 IND_CC-237 98 100 IND_CC-238 100 99 IND_CC-239 71 IND_CC-240 99 95 IND_CC-241 101 95 IND_CC-242 101 94 IND_CC-243 99 100 IND_CC-244 103 99 IND_CC-245 101 100 IND_CC-246 100 99 IND_CC-247 102 99 IND_CC-248 102 90 IND_CC-249 99 99 IND_CC-250 100 94 IND_CC-251 99 100 IND_CC-252 102 100 IND_CC-253 100 100 IND_CC-254 105 97 IND_CC-255 100 100 IND_CC-256 100 99 IND_CC-258 95 100 IND_CC-259 100 99 IND_CC-260 100 100 IND_CC-261 103 100 IND_CC-262 105 100 IND_CC-263 81 100 IND_CC-264 106 97 IND_CC-265 107 88 IND_CC-266 106 98 IND_CC-267 106 86 IND_CC-268 108 99 IND_CC-269 107 100 IND_CC-270 108 100 IND_CC-271 106 100 IND_CC-272 107 99 IND_CC-273 106 99 IND_CC-274 102 8 IND_CC-275 107 100 IND_CC-276 107 100 IND_CC-277 105 100 IND_CC-278 101 35 IND_CC-279 106 100 IND_CC-280 108 100 IND_CC-281 105 84 IND_CC-282 107 69 IND_CC-283 107 96 IND_CC-284 107 100 IND_CC-286 90 IND_CC-287 105 99 IND_CC-288 106 100 IND_CC-289 104 100 IND_CC-290 100 35 IND_CC-291 104 98 IND_CC-292 105 99 IND_CC-293 106 100 IND_CC-294 105 99 IND_CC-295 106 96 IND_CC-296 103 59 IND_CC-297 107 IND_CC-298 74 IND_CC-299 106 27 IND_CC-300 65 IND_CC-301 107 94 IND_CC-302 106 99 IND_CC-303 106 92 IND_CC-304 104 49 IND_CC-305 104 67 IND_CC-306 106 IND_CC-307 103 14 IND_CC-308 106 97 IND_CC-309 104 97 IND_CC-310 104 100 IND_CC-311 83 IND_CC-312 102 44 IND_CC-313 95 IND_CC-314 80 IND_CC-315 101 IND_CC-316 100 IND_CC-317 60 IND_CC-318 100 IND_CC-319 102 IND_CC-320 83 IND_CC-321 95 IND_CC-322 102 IND_CC-323 100 IND_CC-324 98 IND_CC-325 102 IND_CC-326 100 IND_CC-327 101 IND_CC-328 98 IND_CC-329 97 IND_CC-330 67 IND_CC-331 94 IND_CC-332 97 IND_CC-333 92 IND_CC-334 90 IND_CC-335 102 IND_CC-336 103 IND_CC-337 104 IND_CC-338 103 IND_CC-339 103 IND_CC-340 101 IND_CC-341 87 IND_CC-342 103 IND_CC-343 97 IND_CC-344 99 IND_CC-345 105 IND_CC-346 104 IND_CC-347 106 IND_CC-348 102 IND_CC-349 105 IND_CC-350 106 IND_CC-351 99 IND_CC-352 98 IND_CC-353 97 IND_CC-354 84 IND_CC-355 65 IND_CC-356 69 IND_CC-357 95 IND_CC-358 104 IND_CC-359 104 IND_CC-360 69 IND_CC-361 99 IND_CC-362 81 IND_CC-363 74 IND_CC-364 103 IND_CC-365 105 IND_CC-366 104 IND_CC-367 104 IND_CC-368 87 IND_CC-369 74 IND_CC-370 100 IND_CC-371 104 IND_CC-372 105 IND_CC-373 102 IND_CC-374 103 IND_CC-375 59 IND_CC-376 102 IND_CC-377 104 IND_CC-378 104 IND_CC-379 103 IND_CC-380 103 IND_CC-381 104 IND_CC-382 103 IND_CC-383 102 IND_CC-384 104 IND_CC-385 104 IND_CC-386 104 IND_CC-387 104 IND_CC-388 101 IND_CC-389 103 IND_CC-390 100 IND_CC-391 103 IND_CC-392 102 IND_CC-393 103 IND_CC-394 103 IND_CC-395 58 IND_CC-396 81 IND_CC-397 68 IND_CC-398 88 IND_CC-399 101 IND_CC-400 103 IND_CC-401 103 IND_CC-402 102 IND_CC-403 97 IND_CC-404 92 IND_CC-405 96 IND_CC-406 102 IND_CC-407 101 IND_CC-408 101 IND_CC-409 102 IND_CC-410 97 IND_CC-411 101 IND_CC-412 99 IND_CC-413 103 IND_CC-414 102 IND_CC-415 100 IND_CC-416 101 IND_CC-417 102 IND_CC-418 99 IND_CC-419 101 IND_CC-420 100 IND_CC-500 51 IND_CC-501 56 IND_CC-502 71 IND_CC-503 66 IND_CC-504 51 IND_CC-505 67 IND_CC-506 61 IND_CC-507 100 2 IND_CC-508 100 IND_CC-509 101 IND_CC-510 95 IND_CC-511 94 IND_CC-512 92 IND_CC-513 98 IND_CC-514 102 IND_CC-515 104 IND_CC-516 102 IND_CC-517 90 IND_CC-518 86 IND_CC-519 53 IND_CC-520 72 IND_CC-521 66 IND_CC-522 55 IND_CC-523 68 IND_CC-524 62 IND_CC-525 62 IND_CC-526 87 25 IND_CC-527 98 IND_CC-528 102 24 IND_CC-529 104 IND_CC-530 96 IND_CC-531 81 IND_CC-532 62 IND_CC-533 74 IND_CC-534 102 IND_CC-535 90 49 IND_CC-536 54 IND_CC-537 62 IND_CC-538 72 IND_CC-539 75 IND_CC-540 82 IND_CC-541 65 IND_CC-542 104 27 IND_CC-543 102 IND_CC-544 99 IND_CC-545 105 IND_CC-546 99 IND_CC-547 71 IND_CC-548 66 IND_CC-549 60 IND_CC-550 62 IND_CC-551 55 IND_CC-552 68 IND_CC-553 90 −2 IND_CC-554 73 IND_CC-555 91 IND_CC-556 100 7 IND_CC-557 103 IND_CC-558 62 IND_CC-559 56 IND_CC-560 95 IND_CC-561 85 IND_CC-562 104 27 IND_CC-563 92 IND_CC-564 81 IND_CC-565 68 IND_CC-566 90 IND_CC-567 100 IND_CC-568 105 20 IND_CC-569 52 IND_CC-570 57 IND_CC-571 52 IND_CC-572 80 IND_CC-573 100 43 IND_CC-574 101 14 IND_CC-575 78 IND_CC-576 79 IND_CC-577 96 21 IND_CC-578 79 IND_CC-579 57 IND_CC-580 81 IND_CC-581 67 IND_CC-582 58 IND_CC-583 75 IND_CC-584 63 IND_CC-585 52 IND_CC-586 76 IND_CC-587 71 IND_CC-588 61 IND_CC-589 81 IND_CC-590 86 IND_CC-591 62 IND_CC-592 85 IND_CC-593 50 IND_CC-594 91 IND_CC-595 91 IND_CC-596 94 IND_CC-597 101 IND_CC-598 96 IND_CC-599 96 IND_CC-600 100 IND_CC-601 77 IND_CC-602 95 IND_CC-603 75 IND_CC-604 94 IND_CC-605 66 IND_CC-606 66 IND_CC-607 67 IND_CC-608 102 IND_CC-609 101 IND_CC-610 103 IND_CC-611 98 IND_CC-612 65 IND_CC-613 102 IND_CC-614 67 IND_CC-615 67 IND_CC-616 81 IND_CC-617 67 IND_CC-618 61 IND_CC-619 57 IND_CC-620 54 IND_CC-621 67 IND_CC-622 69 IND_CC-623 59 IND_CC-624 62 IND_CC-625 50 IND_CC-626 55 IND_CC-627 54 IND_CC-628 63 IND_CC-629 71 IND_CC-630 53 IND_CC-631 57 IND_CC-632 64 IND_CC-633 86 IND_CC-634 75 IND_CC-635 72 IND_CC-636 79 IND_CC-637 69 IND_CC-638 80 IND_CC-639 78 IND_CC-640 73 IND_CC-641 74 IND_CC-642 77 IND_CC-643 78 IND_CC-644 59 IND_CC-645 78 IND_CC-646 66 IND_CC-647 73 IND_CC-648 78 IND_CC-649 76 IND_CC-650 54 IND_CC-651 76 IND_CC-652 53 IND_CC-653 64 IND_CC-654 60 IND_CC-655 59 IND_CC-656 51 IND_CC-657 66 IND_CC-658 51 IND_CC-659 81 IND_CC-660 50 IND_CC-661 95 IND_CC-662 76 IND_CC-663 85 IND_CC-664 54 IND_CC-665 67 IND_CC-666 78 IND_CC-667 85 IND_CC-668 57 IND_CC-669 60 IND_CC-670 67 IND_CC-671 80 IND_CC-672 88 IND_CC-673 67 IND_CC-674 67 IND_CC-675 87 IND_CC-676 74 IND_CC-677 72 IND_CC-678 82 IND_CC-679 82 IND_CC-680 54 IND_CC-681 53 IND_CC-682 51 IND_CC-683 62 IND_CC-684 67 IND_CC-685 68 IND_CC-686 69 IND_CC-687 76 IND_CC-688 88 IND_CC-689 55 IND_CC-690 85 IND_CC-691 95 IND_CC-692 99 IND_CC-693 68 IND_CC-694 100 IND_CC-695 100 IND_CC-696 102 IND_CC-697 98 IND_CC-698 90 IND_CC-699 75 IND_CC-700 64 IND_CC-701 96 IND_CC-702 80 IND_CC-703 70 IND_CC-704 91 IND_CC-705 101 IND_CC-706 103 IND_CC-707 92 IND_CC-708 99 IND_CC-709 91 IND_CC-710 90 IND_CC-711 94 IND_CC-712 76 IND_CC-713 77 IND_CC-714 51 IND_CC-715 79 IND_CC-716 80 IND_CC-717 72 IND_CC-718 52 IND_CC-719 59 IND_CC-720 80 IND_CC-721 70 IND_CC-722 81 IND_CC-723 55 IND_CC-724 86 IND_CC-725 56 IND_CC-726 67 IND_CC-727 74 IND_CC-728 58 IND_CC-729 76 IND_CC-730 75 IND_CC-731 83 IND_CC-732 100 IND_CC-733 83 IND_CC-734 95 IND_CC-735 81 IND_CC-736 93 IND_CC-737 55 IND_CC-738 89 IND_CC-739 83 IND_CC-740 88 IND_CC-741 100 IND_CC-742 50 IND_CC-743 80 IND_CC-744 71 IND_CC-745 70 IND_CC-746 78 IND_CC-747 59 IND_CC-748 70 IND_CC-749 70 IND_CC-750 99 IND_CC-751 98 IND_CC-752 69 IND_CC-753 90 IND_CC-754 87 IND_CC-755 92 IND_CC-756 104 IND_CC-757 52 IND_CC-758 86 IND_CC-759 78 IND_CC-760 93 IND_CC-761 57 IND_CC-762 55 IND_CC-763 74 IND_CC-764 71 IND_CC-765 105 IND_CC-766 93 IND_CC-767 73 IND_CC-768 79 IND_CC-769 91 IND_CC-770 109 IND_CC-771 108 IND_CC-772 52 IND_CC-773 80 IND_CC-774 81 IND_CC-775 98 IND_CC-776 99 IND_CC-777 83 IND_CC-778 105 IND_CC-779 69 IND_CC-780 101 IND_CC-781 106 IND_CC-782 107 IND_CC-783 102 IND_CC-784 99 IND_CC-785 98 IND_CC-786 104 IND_CC-787 93 IND_CC-788 71 IND_CC-789 98 IND_CC-790 96 IND_CC-791 91 IND_CC-792 89 IND_CC-793 79 IND_CC-794 59 IND_CC-795 54 IND_CC-796 66 IND_CC-797 91 IND_CC-798 71 IND_CC-799 52 IND_CC-800 97 IND_CC-801 92 IND_CC-802 89 IND_CC-803 76 IND_CC-804 61 IND_CC-805 51 IND_CC-806 75 IND_CC-807 53

The foregoing description and examples have been set forth merely to illustrate the invention and are not intended to be limiting. Since modifications of the described embodiments incorporating the spirit and substance of the invention may occur to persons skilled in the art, the invention should be construed broadly to include all variations within the scope of the appended claims and equivalents thereof. 

1. A substituted spiro-amide compound corresponding to formula (I)

wherein a represents 0 or 1; t represents 1, 2 or 3; b represents 0, 1 or 2; c, d, e and f each independently represent 0, 1 or 2; D represents one of the following groups D1 or D2

q represents 0 or 1; represents 0 or 1; r represents 1, 2 or 3; B represents C(═O), S(═O)₂ or the group —C(═O)—N(R⁹), wherein the nitrogen atom thereof is bonded to R¹; Q₁ and Q₂ each independently represent C, CH or N; R¹ represents C₁₋₆-alkyl, aryl, heteroaryl, —CH(aryl)₂, C₃₋₈-cycloalkyl or an aryl, heteroaryl or C₃₋₈-cycloalkyl bonded via a C₁₋₆-alkylene group, C₂₋₆-alkenylene group or C₂₋₆-alkynylene group, or an aryl or heteroaryl group bonded via a C₃₋₆ cycloalkylene group; R² represents H, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₆-alkylene group; R³ and R⁴ together with the group -Q₁-Q₂- joining them form a 4-, 5-, 6- or 7-membered ring, which may be unsubstituted or substituted on one or more of its carbon ring members by one or more substituents independently selected from the group consisting of F, Cl, Br, I, CF₃, C₁₋₆-alkyl, O—C₁₋₆-alkyl, OH, OCF₃, SH, SCF₃, aryl and heteroaryl and/or optionally may be fused with at least one aryl or heteroaryl, wherein the ring may be saturated, unsaturated one or more times or aromatic, and may optionally contain one or more hetero atoms or hetero atom groups independently selected from the group consisting of N, NR⁵⁰, O, S, S(═O) and S(═O)₂; wherein R⁵⁰ denotes H, C₁₋₆-alkyl, —C(═O)—R⁵¹, C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₃-alkylene group, and R⁵¹ denotes C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₃-alkylene group; R⁵ represents 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of F, Cl, CF₃, OCF₃, OH, C₁₋₆-alkyl and O—C₁₋₆-alkyl, or two adjacent substituents R⁵ form a fused-on aryl, heteroaryl or C₄₋₈-cycloalkyl ring; or two substituents R⁵ bonded to a carbon atom form a 3, 4 or 5 membered saturated carbocyclic ring, which may be unsubstituted or substituted on one or more of its carbon ring members by one or more substituents independently selected from the group consisting of F, CF₃ and C₁₋₆-alkyl; R⁶ represents 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of F, Cl, Br, CF₃, OCF₃, OH, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, O—C₁₋₆-alkyl, NO₂, NH₂, N(H)(C₁₋₆-alkyl) and N(C₁₋₆-alkyl)₂, or two adjacent substituents R⁶ form a fused-on aryl, heteroaryl or C₄₋₈-cycloalkyl ring; R⁷ and R⁸ each independently represent 0, 1, 2, 3 or 4 substituents each independently selected from the group consisting of F, Cl, OH, ═O, C₁₋₆-alkyl, O—C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl, heteroaryl and a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₆-alkylene group, or two adjacent substituents R⁷ or R⁸ form a fused-on aryl or heteroaryl ring; R⁹ represents H, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₃-alkylene group; X represents CR^(10a)R^(10b), NR¹¹ or O; Y represents CR^(12a)R^(12b), NR¹³ or O; with the proviso that X does not denote NR¹¹ if Y is NR¹³; and with the proviso that X and Y do not simultaneously denote O; wherein R^(10a), R^(10b), R^(12a) and R^(12b) each independently denote H, F, Cl, OH, C₁₋₆-alkyl, O—C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl or heteroaryl, or represent a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₆-alkylene group; or R^(10a) and R^(10b) together can represent ═O; or R^(12a) and R^(12b) together can represent ═O; R¹¹ and R¹³ each independently represent H, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl or heteroaryl, or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₆-alkylene group; Z represents CR^(14a)R^(14b), NR¹⁵ or O; R^(14a) represents H, NR¹⁶R¹⁷, C₁₋₆-alkylene-NR¹⁶R¹⁷, O—C₁₋₆-alkylene-NR¹⁶R¹⁷, C(═O)—NR¹⁶R¹⁷, C(═O)—C₁₋₆-alkylene-NR¹⁶R¹⁷, OR¹⁸, C₁₋₆-alkylene-OR¹⁸, C₁₋₆-alkylene-O—C₁₋₆-alkylene-OR¹⁸, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, heterocyclyl, aryl or heteroaryl, or denotes a C₃₋₈-cycloalkyl, heterocyclyl, aryl or heteroaryl group bonded via a C₁₋₆-alkylene group, R^(14b) represents H, NR¹⁶R¹⁷, C₁₋₆-alkylene-NR¹⁶R¹⁷, O—C₁₋₆-alkylene-NR¹⁶R¹⁷, C(═O)—NR¹⁶R¹⁷, C(═O)—C₁₋₆-alkylene-NR¹⁶R¹⁷, OR¹⁸, C₁₋₆-alkylene-OR¹⁸, C₁₋₆-alkylene-O—C₁₋₆-alkylene-OR¹⁸, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, heterocyclyl, aryl or heteroaryl, or denotes a C₃₋₈-cycloalkyl, heterocyclyl, aryl or heteroaryl group bonded via a C₁₋₆-alkylene group, R¹⁵ represents H, —C(═O)—R¹⁹, —S(═O)₂—R¹⁹, —C(═O)—N(R²⁰)—R¹⁹, CHR²⁵R²⁶, C₁₋₁₀-alkyl, C₃₋₈-cycloalkyl, heterocyclyl, aryl or heteroaryl or denotes a CHR²⁵R²⁶, C₃₋₈-cycloalkyl, heterocyclyl, aryl or heteroaryl group bonded via a C₁₋₆-alkylene group; R¹⁶ and R¹⁷ each independently represent H, C₁₋₆-alkyl or C₃₋₈-cycloalkyl, or R¹⁶ and R¹⁷ together with the nitrogen atom to which they are bound form a 4-, 5-, 6- or 7-membered heterocyclic ring, which may be unsubstituted or substituted on one or more of its carbon ring members by one or more substituents independently selected from the group consisting of F, Cl, Br, I, CF₃, C₁₋₆-alkyl, O—C₁₋₆-alkyl, OH, OCF₃, SH, SCF₃, NR^(A)R^(B), aryl and heteroaryl and/or optionally may be fused with at least one aryl or heteroaryl ring, wherein the heterocyclic ring may be saturated or unsaturated one or more times, and may optionally contain one or more hetero atoms or hetero atom groups independently selected from the group consisting of N, NR^(50a), O, S, S(═O) and S(═O)₂; wherein R^(50a) denotes H, C₁₋₆-alkyl, —C(═O)—R^(51a), C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₃-alkylene group, and R^(51a) denotes C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₃-alkylene group; R¹⁸ represents H, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, heterocyclyl, aryl, heteroaryl or C₂₋₆-alkylene-NR¹⁶R¹⁷ or denotes a heterocyclyl, C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₆-alkylene group; R¹⁹ represents C₁₋₆-alkyl, aryl, heteroaryl, —CH(aryl)₂, C₃₋₈-cycloalkyl, heterocyclyl or an aryl, heteroaryl, C₃₋₈-cycloalkyl or heterocyclyl group bonded via a C₁₋₆-alkylene group, C₂₋₆-alkenylene group or C₂₋₆-alkynylene group; R²⁰ represents H, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₃-alkylene group; or if X represents O and f represents 0, then Z may denote —(C(R²¹)—C(R²²))—, wherein R²¹ and R²² together with the carbon atoms joining them form a fused-on aryl or heteroaryl ring; or if X represents O and f represents 0, then Z may denote ═(N(CR²³))—, wherein the N atom is bonded to the O atom via a single bond, and R²³ represents H, C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl or heteroaryl or denotes a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₆-alkylene group; R²⁵ and R²⁶ each independently represent H, C₁₋₄-alkyl, C₃₋₈-cycloalkyl, aryl or heteroaryl, or R²⁵ and R²⁶ together with the CH grouping joining them form a 4-, 5-, 6- or 7-membered ring, which may be unsubstituted or substituted on one or more of its carbon ring members by one or more substituents independently selected from the group consisting of F, Cl, Br, I, CF₃, C₁₋₆-alkyl, O—C₁₋₆-alkyl, OH, OCF₃, SH, SCF₃, NR^(A)R^(B), aryl and heteroaryl, wherein the ring may be saturated or unsaturated one or more times, but is not aromatic, and optionally may contain one or more hetero atoms or hetero atom groups independently selected from the group consisting of N, NR^(50b), O, S, S(═O) and S(═O)₂; wherein R^(50b) denotes H, C₁₋₆-alkyl, —C(═O)—R^(51b), C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₃-alkylene group, and R^(51b) denotes C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₃-alkylene group; R^(A) and R^(B) each independently represent H, C₁₋₆-alkyl or C₃₋₈-cycloalkyl, or R^(A) and R^(B) together with the nitrogen atom to which they are bound form a 4-, 5-, 6- or 7-membered heterocyclic ring, which may be unsubstituted or substituted on one or more of its carbon ring members by one or more substituents independently selected from the group consisting of F, Cl, Br, I, CF₃, C₁₋₆-alkyl, O—C₁₋₆-alkyl, OH, OCF₃, SH, SCF₃, aryl and heteroaryl, wherein the heterocyclic ring may be saturated or unsaturated one or more times, but is not aromatic, and optionally may contain one or more hetero atoms or hetero atom groups independently selected from the group consisting of N, NR^(C), O, S, S(═O) and S(═O)₂; wherein R^(C) denotes H, C₁₋₆-alkyl, —C(═O)—R^(D), C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₃-alkylene group, and R^(D) denotes C₁₋₆-alkyl, C₃₋₈-cycloalkyl, aryl, heteroaryl or a C₃₋₈-cycloalkyl, aryl or heteroaryl group bonded via a C₁₋₃-alkylene group; wherein the aforementioned C₁₋₄-alkyl, C₁₋₆-alkyl, C₁₋₁₀-alkyl, C₁₋₃-alkylene, C₁₋₆-alkylene, C₂₋₆-alkylene, C₂₋₆-alkenylene, C₂₋₆-alkynylene, C₃₋₈-cycloalkyl, C₄₋₈-cycloalkyl, heterocyclyl, aryl and heteroaryl groups may each be unsubstituted or substituted one or more times by identical or different substituents, and the abovementioned C₁₋₄-alkyl, C₁₋₆-alkyl, C₁₋₁₀-alkyl, C₁₋₃-alkylene, C₁₋₆-alkylene, C₂₋₆-alkylene, C₂₋₆-alkenylene and C₂₋₆-alkynylene groups may each be branched or unbranched; or a physiologically acceptable salt thereof.
 2. A compound as claimed in claim 1, wherein said compound is in the form of an isolated stereoisomer.
 3. A compound as claimed in claim 1, wherein said compound is in the form of a mixture of stereoisomers in any mixing ratio.
 4. A compound as claimed in claim 3, wherein said mixture is a racemic mixture.
 5. A compound as claimed in claim 1, wherein the partial structure (Ac)

represents a partial structure selected from the group consisting of:


6. A compound as claimed in claim 1, wherein D represents a group D1 selected from the group consisting of:


7. A compound as claimed in claim 1, wherein R¹ represents C₁₋₆-alkyl, —CH(phenyl)₂, C₃₋₈-cycloalkyl, phenyl, naphthyl, chromanyl, indolyl, benzofuranyl, benzothiophenyl, benzooxazolyl, benzooxadiazolyl, pyrrolyl, furanyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, imidazothiazolyl, carbazolyl, dibenzofuranyl, dibenzothiophenyl or a phenyl or naphthyl group bonded via a C₁₋₃-alkylene group, a C₂₋₃-alkenylene group or a C₂₋₃-alkynylene group; wherein the aforementioned aryl or heteroaryl groups may each be unsubstituted or substituted one or more times by identical or different substituents independently selected from the group consisting of O—C₁₋₃-alkyl, C₁₋₆-alkyl, F, Cl, Br, I, CF₃, OCF₃, OH, SH, phenyl, phenoxy, naphthyl, furyl, thienyl and pyridinyl, and wherein the aforementioned alkyl, alkylene, alkenylene and alkynylene groups may each be unsubstituted or substituted one or more times by identical or different substituents independently selected from the group consisting of O—C₁₋₃-alkyl, F, Cl, Br, I, CF₃, OCF₃, OH, SH, phenyl, phenoxy, naphthyl, furyl, thienyl and pyridinyl.
 8. A compound as claimed in claim 7, wherein R¹ represents C₁₋₄-alkyl, —CH(phenyl)₂, C₃₋₆-cycloalkyl, phenyl, naphthyl, chromanyl, benzothiophenyl, benzooxadiazolyl, thienyl, pyridinyl, imidazothiazolyl, dibenzofuranyl or a phenyl bonded via a C₁₋₃-alkylene group or a C₂₋₃-alkenylene group.
 9. A compound as claimed in claim 1, wherein R² represents H, —CF₃, —CH₂—CF₃, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
 10. A compound as claimed in claim 1, wherein R⁹ represents H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
 11. A compound as claimed in claim 1, wherein D represents a group D2 selected from the group consisting of:

wherein R³⁰⁰ represents 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of F, Cl, Br, I, CF₃, O—CF₃, C₁₋₄-alkyl and O—C₁₋₄-alkyl; R³¹⁰ represents 0, 1, 2 or 3 substituents independently selected from the group consisting of F, Cl, Br, I, CF₃, O—CF₃, C₁₋₄-alkyl and O—C₁₋₄-alkyl; R³²⁰ represents a substituent selected from the group consisting of H, F, Cl, Br, I, CF₃, O—CF₃ and C₁₋₄-alkyl; R³³⁰ represents a substituent selected from the group consisting of H, C₁₋₄-alkyl, aryl, CH₂-aryl and heteroaryl; r1 represents 1 or 2, and r2 represents 1 or
 2. 12. A compound as claimed in claim 1, wherein the following partial structure (SP)

is selected from the group consisting of:

wherein R¹²⁰ represents 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of F, Cl, OCF₃, CF₃, CN, methyl and methoxy.
 13. A compound as claimed in claim 1, wherein R^(14a) represents H, aryl, heteroaryl, C₁₋₃-alkylene-aryl or C₁₋₃-alkylene-heteroaryl; R^(14b) represents aryl, heteroaryl, C₁₋₃-alkylene-aryl, C₁₋₃-alkylene-heteroaryl, NR¹⁶R¹⁷, C₁₋₃-alkylene-NR¹⁶R¹⁷, C(═O)—NR¹⁶R¹⁷, OR³⁵ or C₁₋₃-alkylene-OR³⁵; R¹⁶ and R¹⁷ each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or R¹⁶ and R¹⁷ together with the nitrogen atom to which they are bound form a structure selected from the group consisting of:

R²⁸ represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl; R³³ represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl, O—C₁₋₃-alkyl and NR^(34a)R^(34b); R^(34a) and R^(34b) each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or R^(34a) and R^(34b) together with the nitrogen atom to which they are bound form a structure selected from the group consisting of:

R³⁹ represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl and O—C₁₋₃-alkyl; R⁴⁰ represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl; R³⁵ represents H, C₁₋₆-alkyl, C₃₋₆-cycloalkyl, aryl, heteroaryl, C₁₋₃-alkylene-C₃₋₆-cycloalkyl, C₁₋₃-alkylene-aryl, C₁₋₃-alkylene-heteroaryl or the group

 wherein p represents 1, 2 or 3, R⁴¹ and R⁴² each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or R⁴¹ and R⁴² together with the nitrogen atom to which they are bound form a structure selected from the group consisting of:

R⁴³ represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl, O—C₁₋₃-alkyl and NR^(45a)R^(45b); R⁴⁴ represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl; R^(45a) and R^(45b) each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or R^(45a) and R^(45b) together with the nitrogen atom to which they are bound form a structure selected from the group consisting of:

R⁴⁶ represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl and O—C₁₋₃-alkyl; and R⁴⁷ represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl.
 14. A compound as claimed in claim 1, wherein R¹⁵ represents H, C₁₋₆-alkyl, —CHR²⁵R²⁶, C₁₋₃-alkylene-CHR²⁵R²⁶, aryl, heteroaryl, C₁₋₃-alkylene-aryl, C₁₋₃-alkylene-heteroaryl, —C(═O)—R¹⁹, —S(═O)₂—R¹⁹ or the group —C(═O)—N(R²⁰)—R¹⁹; R²⁵ and R²⁶ each independently represent H, C₁₋₄-alkyl, C₃₋₆-cycloalkyl, aryl or heteroaryl, or R²⁵ and R²⁶ together with the CH group joining them form a structure selected from the group consisting of:

R²⁷ represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl, O—C₁₋₃-alkyl and NR^(48a)R^(48b); R^(28a) represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, aryl and heteroaryl; R^(48a) and R^(48b) each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, R^(48a) and R^(48b) together with the nitrogen atom to which they are bound form a structure selected from the group consisting of:

R⁴⁹ represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl₁, CF₃, OCF₃, C₁₋₆-alkyl and O—C₁₋₃-alkyl; R⁵² represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl; R¹⁹ represents C₁₋₆-alkyl, aryl, heteroaryl, —CH(aryl)₂, C₃₋₈-cycloalkyl, heterocyclyl or an aryl, heteroaryl, C₃₋₈-cycloalkyl or heterocyclyl group bonded via a C₁₋₆-alkylene group, C₂₋₆-alkenylene group or C₂₋₆-alkynylene group; and R²⁰ represents H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
 15. A compound as claimed in claim 1, wherein the following partial structure (SP)

is selected from the group consisting of:

wherein z represents 1, 2 or 3; o1 represents 1; R⁶⁰ in each case represents (het)aryl or C₁₋₃-alkylene-(het)aryl; R²⁵ and R²⁶ each independently represent H, C₁₋₆-alkyl, C₃₋₆-cycloalkyl or (het)aryl, or R²⁵ and R²⁶ together with the CH to which they are bound form a structure selected from the group consisting of:

R²⁷ represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl, O—C₁₋₃-alkyl and NR^(48a)R^(48b); R^(28a) represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl and het(aryl); R^(48a) and R^(48b) each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, R^(48a) and R^(48b) together with the nitrogen atom to which they are bound form a structure selected from the group consisting of:

R⁴⁹ represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl and O—C₁₋₃-alkyl; R⁵² represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and (het)aryl; G represents C(═O), S(═O)₂ or the group —C(═O)—N(R²⁰), wherein the nitrogen atom thereof is bonded to R¹⁹, R¹⁹ represents C₁₋₆-alkyl, (het)aryl, —CH(aryl)₂, C₃₋₈-cycloalkyl, heterocyclyl or a (het)aryl, C₃₋₈-cycloalkyl or heterocyclyl bonded via a C₁₋₆-alkylene group, C₂₋₆-alkenylene group or C₂₋₆-alkynylene group; R²⁰ represents H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; R¹⁶ and R¹⁷ each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or R¹⁶ and R¹⁷ together with the nitrogen atom to which they are bound form a structure selected from the group consisting of

R²⁸ represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and (het)aryl; R³³ represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl, O—C₁₋₃-alkyl and NR^(34a)R^(34b); R^(34a) and R^(34b) each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or R^(34a) and R^(34b) together with the nitrogen atom to which they are bound form a structure selected from the group consisting of:

R³⁹ represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl and O—C₁₋₃-alkyl; R⁴⁰ represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl; R³⁵ represents H, C₁₋₆-alkyl, C₃₋₆-cycloalkyl, (het)aryl or a C₃₋₆-cycloalkyl or (het)aryl group bonded via a C₁₋₃-alkylene group; R³⁶ represents (het)aryl or C₁₋₃-alkylene-(het)aryl; R³⁷ represents H, C₁₋₆-alkyl or for the group

 wherein p represents 1,2 or 3, wherein R⁴¹ and R⁴² each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or R⁴¹ and R⁴² together with the nitrogen atom to which they are bound form a structure selected from the group consisting of

R⁴³ represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl, O—C₁₋₃-alkyl and NR^(45a)R^(45b); R⁴⁴ represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl; R^(45a) and R^(45b) each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or R^(45a) and R^(45b) together with the nitrogen atom to which they are bound form a structure selected from the group consisting of:

R⁴⁶ represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl and O—C₁₋₃-alkyl; R⁴⁷ represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl, and het(aryl) in each case represents a group selected from the group consisting of:

wherein R¹⁰⁰ represents 0, 1, 2 or 3 substituents each independently selected from the group consisting of F, Cl, CF₃, OCF₃, OH, O—C₁₋₆-alkyl, SH, S—C₁₋₆-alkyl, C₁₋₆-alkyl, C₃₋₆-cycloalkyl, O—C₃₋₆-cycloalkyl, NR⁶¹R⁶², C(═O)—NR⁶¹R⁶², phenyl, pyridyl, pyrimidyl, or OCF₃, OH, O—C₁₋₆-alkyl, SH, S—C₁₋₆-alkyl, C₃₋₆-cycloalkyl, O—C₃₋₆-cycloalkyl, NR⁶¹R⁶², C(═O)—NR⁶¹R⁶², phenyl, pyridyl or pyrimidyl bonded via a C₁₋₆-alkylene group; R⁶¹ and R⁶² each independently represent H, C₁₋₆-alkyl or C₃₋₆-cycloalkyl, or R⁶¹ and R⁶² together with the nitrogen atom to which they are bound form a structure selected from the group consisting of:

R⁶³ represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF₃, OCF₃, C₁₋₆-alkyl and O—C₁₋₃-alkyl; R⁶⁴ represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; and R³⁵⁰ represents H, CF₃, phenyl, pyridyl, pyrimidyl or a phenyl, pyridyl or pyrimidyl group bonded via a C₁₋₆-alkylene group.
 16. A compound as claimed in claim 1, wherein the following partial structure (SP):

is selected from the group consisting of:


17. A compound as claimed in claim 1, selected from the group consisting of: [H-01] 7-chloro-2-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, [H-02] 2-chloro-N-[6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-03] 4-methoxy-2,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [H-04] 2-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.4]nonane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-05] 2-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-06] N-[6-[9-(azetidin-1-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide, [H-07] 2-chloro-N-[6-[9-(3,3-difluoro-azetidin-1-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-08] 2-chloro-N-[6-(9-pyridin-4-yloxy-3-azaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-09] 2-chloro-N-[(1R)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-10] 2-chloro-N-[(1S)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-11] 2-chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-12] 2-chloro-N-[(1S)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-13] 7-chloro-2-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-2,3-dihydro-isoindol-1-one, [H-14] 7-chloro-2-[(1R)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-2,3-dihydro-isoindol-1-one, [H-15] 7-chloro-2-[(1S)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-2,3-dihydro-isoindol-1-one, [H-16] 4-methoxy-2,6-dimethyl-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic acid amide, [H-17] -methoxy-2,6-dimethyl-N-[(1R)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic acid amide, [H-18] 4-methoxy-2,6-dimethyl-N-[(1S)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic acid amide, [H-19] 4-methoxy-2,6-dimethyl-N-[(1S)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic acid amide, [H-20] 2-chloro-N-[(1S)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-21] 2-chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [H-22] 2-chloro-N-[(1R)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-23] 2-chloro-N-[(1S)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [H-24] 2-chloro-N-[(1S)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-25] 2-chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [H-26] 2-chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-27] 2-chloro-N-[(1R)-6-(7-pyridin-4-yl-2,7-diazaspiro[3.5]nonane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-28] 2-chloro-N-[(1R)-6-[9-(1-methyl-piperidin-4-yl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-29] 2-chloro-N-[(1R)-6-[9-(4-methyl-piperazine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-31] 2-chloro-N-[(1R)-6-[9-[(1-methyl-piperidin-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-32] 2-chloro-N-[(1R)-6-(spiro[1H-furo[3,4-c]pyridine-3,4′-piperidine]-1′-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-33] 2-chloro-N-[(1R)-6-(8-pyridin-4-yl-4,8-diazaspiro[5.5]undecane-4-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-34] 2-chloro-N-[(1R)-6-(7-pyridin-4-yl-3,7-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-35] 2-chloro-N-[(1R)-6-(2-pyridin-4-yl-2,9-diazaspiro[4.5]decane-9-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-36] N-[(1R)-6-[9-(4-tert-butyl-piperazin-1-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide, [H-37] 2-chloro-N-[(1R)-6-[9-(pyrrolidine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-38] 2-chloro-N-[(1R)-6-[8-(2-pyrrolidin-1-yl-acetyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-39] 2-chloro-N-[6-(8-pyridin-2-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-40] 2-chloro-N-[6-[8-(4-chlorophenyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-41] 2-chloro-N-[6-[8-(4-fluorophenyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-42] 2-chloro-N-[6-[8-[4-(trifluoromethyl)-phenyl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-43] 2-chloro-N-[6-(8-pyridin-3-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-44] 2-chloro-N-[6-(8-pyrimidin-2-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-45] 2-chloro-N-[6-[8-[2-(trifluoromethyl)-pyridin-4-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-46] 2-chloro-N-[6-[8-[8-(trifluoromethyl)-quinolin-4-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-47] 2-chloro-N-[2,2-dimethyl-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide, [H-48] 2-chloro-N-[6-[8-[5-(trifluoromethyl)-pyridin-2-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-49] 2-chloro-N-methyl-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-50] 2-chloro-N-[6-(8-isoquinolin-6-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-51] 2-chloro-N-[6-[8-[2-(trifluoromethyl)-pyrimidin-4-yl]-3,8-diazaspiro[4.5]-decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-52] N-[(5R)-1-Azabicyclo[2.2.2]octan-5-yl]-3-[(3R)-3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-3-azaspiro[5.5]undecane-9-carboxylic acid amide, [H-53] 2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-54] 2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-2,9-diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-55] 2-Chloro-N-[(1R)-6-[9-(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazin-7-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-56] 6-Methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-naphthalene-2-carboxylic acid amide, [H-57] 2-Chloro-N-[(4R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, [H-58] 2-Chloro-N-[(4R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, [H-59] 2-Chloro-N-[(1R)-5-methyl-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-60] 2-Chloro-4-methoxy-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-61] 4-Methoxy-2-methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-62] N-[(5S)-1-Azabicyclo[2.2.2]octan-5-yl]-3-[(3R)-3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-3-azaspiro[5.5]undecane-9-carboxylic acid amide, [H-63] 2-Chloro-4-methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-64] 2-Chloro-N-[(1R)-5-fluoro-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide hydrochloride, [H-65] 2-Chloro-N-[(4R)-7-fluoro-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, [H-66] 2-Chloro-N-[(1R)-5-methyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-67] 2-Chloro-N-[(4R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, [H-68] 6-Methoxy-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-naphthalene-2-carboxylic acid amide, [H-69] 2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-4,8-diazaspiro[5.5]undecane-4-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-70] 2-Chloro-N-[(1R)-7-(2-pyridin-4-yl-2,9-diazaspiro[4.5]decane-9-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-71] 2-Chloro-N-[(1R)-7-(7-pyridin-4-yl-2,7-diazaspiro[3.5]nonane-2-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-72] 2-Chloro-N-[(1R)-7-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-73] 2-Chloro-N-[(4R)-8-fluoro-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, [H-74] 2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyloxy)-benzamide, [H-75] 2-Methyl-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyloxy)-benzamide, [H-76] 2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide, [H-77] 2-Chloro-N-[(4R)-8-fluoro-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, [H-78] 2-Chloro-N-[(4R)-8-fluoro-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, [H-79] 2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.4]nonane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-80] 2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-81] 2-Chloro-N-[(1R)-7-(7-pyridin-4-yl-3,7-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-82] 2-Chloro-N-[(1R)-6-fluoro-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-83] 2-Chloro-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide, [H-84] N-[(1R)-6-(8-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyrimidine-5-carboxylic acid amide, [H-85] 2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide, [H-86] N-[(1R)-6-(3-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyrimidine-5-carboxylic acid amide, [H-87] 2-Chloro-N-[(1R)-6-fluoro-7-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-88] 2-Chloro-N-[(1R)-6-fluoro-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide, [H-89] 2-Chloro-N-[(1R)-5-fluoro-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-90] 2-Chloro-N-[(1R)-5-fluoro-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-91] 2-Chloro-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-92] 2-Chloro-N-[(4R)-7-fluoro-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, [H-93] 2-Chloro-N-[(1R)-5-methyl-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-94] 2,3-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-95] 2,3-Dichloro-N-[(1R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-96] 7-Chloro-2-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, [H-97] 2-Chloro-N-[(1R)-6-[9-(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine-7-carbonyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-98] 2,5-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-99] 2,6-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-100] 2,6-Dichloro-N-[(1R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-101] 2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-102] 2-Fluoro-N-[(1R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-103] 4-Methoxy-2,5-dimethyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-104] 2,6-Dimethyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-105] 2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [H-106] 2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic acid amide, [H-107] 2-Chloro-N-[(4R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide, [H-108] 2-Fluoro-4-methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-109] 2-Chloro-6-fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-110] 2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide, [H-111] 2-Chloro-N-[(1R)-6-[8-(2,6-dimethyl-pyridin-4-yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide hydrochloride, [H-112] 2-Chloro-N-[(1R)-6-[8-(2-methyl-pyridin-4-yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-113] 2,3-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [H-114] 2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-3-carboxylic acid amide, [H-115] N-[(1R)-6-(8-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyl)-pyridine-3-carboxylic acid amide, [H-116] 2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [H-117] 2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [H-118] N-[(1R)-6-(8-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzenesulfonic acid amide, [H-119] 2,6-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [H-120] 2-Chloro-N-[6-[9-[2-(1H-imidazol-1-yl)-ethoxy]-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-128] 2-Chloro-N-[6-(8-hydroxy-8-pyridin-4-yl-3-azaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-129] 2-Chloro-N-[6-[8-(1-oxido-pyridin-1-ium-4-yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-130] 2-Chloro-N-[6-[8-[5-(trifluoromethyl)-pyrimidin-2-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-131] 2-Chloro-N-[6-[9-(1H-imidazol-1-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-132] 2-Chloro-N-[3,3-dimethyl-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide, [H-133] 2-Chloro-N-[6-(8-pyridin-4-yl-3-azaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-134] 5-Methyl-2-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1,2-dihydro-pyrrolo[2,1-e]imidazol-3-one, [H-135] 2-Chloro-N-[(1R)-6-(8-pyridin-3-yl-3-azaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-136] 2-Chloro-N-methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [H-137] 2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-N-(2,2,2-trifluoro-ethyl)-benzamide, [H-138] 2-Chloro-N-[6-(3-pyridin-4-yl-3,10-diazaspiro[5.6]dodecane-10-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-139] 2-Chloro-N-[(1R)-6-[8-(4-methoxyphenyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-140] 2-Chloro-N-[(1R)-6-[8-(4-cyano-phenyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-141] 2-Chloro-5-fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-142] 2,5-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [H-143] 3-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide, [H-144] 4-Methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzenesulfonic acid amide, [H-145] 2-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide, [H-146] 2-(2-Chlorophenyl)-2-methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide, [H-147] 4-Methoxy-2-methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [H-148] 1-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopropane-1-carboxylic acid amide, [H-149] 2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzenesulfonic acid amide, [H-150] 1-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide, [H-151] 2-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, [H-152] 2-(2-Fluorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, [H-153] 2-Chloro-3-fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-154] 2-(o-Tolyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, [H-155] 2-Chloro-N-[(1S)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-156] 2-Chloro-N-[(1S)-5-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-157] 7-Chloro-2-[(1S)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbo dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, [H-158] 7-Chloro-2-[(1S)-5-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl) 2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, [H-159] 7-Chloro-2-[(1R)-5-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, [H-160] 7-Chloro-2-[(1R)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbo dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, [H-161] 2-Chloro-N-[(1S)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-162] 2-Chloro-N-[(1R)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-163] 2-Chloro-N-[(1S)-4-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-164] 2-Chloro-N-[(1R)-4-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-165] 2-Chloro-N-[(1S)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [H-166] 2-Chloro-N-[(1R)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [H-167] 2-Chloro-N-[(1R)-4-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [H-168] 7-Chloro-2-[(1S)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbo dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, [H-169] 7-Chloro-2-[(1R)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbo dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, [H-170] 7-Chloro-2-[(1R)-4-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one, [H-171] 2-Chloro-N-[(1R)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-172] 2-Chloro-N-[(1R)-5-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [H-173] 2-Chloro-N-[(1R)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [Ind_CC-001] 4-methoxy-2,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [Ind_CC-002] N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic acid amide, [Ind_CC-003] N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide, [Ind_CC-004] 3-chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-005] 5-chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-006] 2,4-dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-007] 2-(2-chlorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, [Ind_CC-008] (E)-3-(2-chlorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acrylamide, [Ind_CC-009] 2-(2-chlorophenyl)-2-phenyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, [Ind_CC-010] 2-chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [Ind_CC-011] 1-(3,4-dichlorophenyl)-3-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, [Ind_CC-012] 1-[(2-chlorophenyl)-methyl]-3-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, [Ind_CC-013] 4-methoxy-2,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-014] N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic acid amide, [Ind_CC-015] N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide, [Ind_CC-016] 3-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-017] 5-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-018] 2,4-dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-019] 2-(2-chlorophenyl)-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, [Ind_CC-020] (E)-3-(2-chlorophenyl)-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acrylamide, [Ind_CC-021] 2-(2-chlorophenyl)-N-methyl-2-phenyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, [Ind_CC-022] 3-(3,4-dichlorophenyl)-1-methyl-1-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, [Ind_CC-023] 3-[(2-chlorophenyl)-methyl]-1-methyl-1-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, [Ind_CC-024] 2-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [Ind_CC-025] 4-methoxy-N,2,6-trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [Ind_CC-026] 4-methoxy-N,2,6-trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-027] N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic acid amide, [Ind_CC-028] 2-(trifluoromethyl)-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-029] 3-chloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-030] 5-chloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-031] 2,4-dichloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-032] 2-(2-chlorophenyl)-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-acetamide, [Ind_CC-033] (E)-3-(2-chlorophenyl)-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-acrylamide, [Ind_CC-034] 2-chloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [Ind_CC-035] 4-methoxy-2,6-dimethyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [Ind_CC-036] 1-(3,4-dichlorophenyl)-3-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-urea, [Ind_CC-037] 1-[(2-chlorophenyl)-methyl]-3-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-urea, [Ind_CC-038] 2-(2-chlorophenyl)-2-phenyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-acetamide, [Ind_CC-039] 4-methoxy-2,6-dimethyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-040] N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic acid amide, [Ind_CC-041] N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide, [Ind_CC-042] 3-chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-043] 5-chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-044] 2,4-dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-045] 2-(2-chlorophenyl)-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, [Ind_CC-046] (E)-3-(2-chlorophenyl)-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acrylamide, [Ind_CC-047] 1-(3,4-dichlorophenyl)-3-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, [Ind_CC-048] 1-[(2-chlorophenyl)-methyl]-3-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, [Ind_CC-049] 2-chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [Ind_CC-050] 4-methoxy-2,6-dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [Ind_CC-051] 2-(2-chlorophenyl)-2-phenyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, [Ind_CC-052] N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-pyridine-2-carboxylic acid amide, [Ind_CC-053] 2-(2-chlorophenyl)-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-acetamide, [Ind_CC-054] 5-chloro-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-055] 3-chloro-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-056] 2-(2-chlorophenyl)-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro-[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-2-phenyl-acetamide, [Ind_CC-057] 1-(3,4-dichlorophenyl)-3-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-urea, [Ind_CC-058] N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-2-(trifluoromethyl)-benzamide, [Ind_CC-059] 2,4-dichloro-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide, [Ind_CC-060] (E)-3-(2-chlorophenyl)-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-acrylamide, [Ind_CC-061] 1-[(2-chlorophenyl)-methyl]-3-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-urea, [Ind_CC-062] 2-chloro-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-benzenesulfonic acid amide, [Ind_CC-063] N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide, [Ind_CC-064] N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-(trifluoromethyl)-benzamide, [Ind_CC-065] 3-chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-066] 5-chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-067] 2,4-dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide, [Ind_CC-068] N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-methoxy-2,6-dimethyl-benzamide, [Ind_CC-069] 2-(2-chlorophenyl)-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-acetamide, [Ind_CC-070] (E)-3-(2-chlorophenyl)-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-acrylamide, [Ind_CC-071] 1-(3,4-dichlorophenyl)-3-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-urea, [Ind_CC-072] 2-chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzenesulfonic acid amide, [Ind_CC-073] 1-[(2-chlorophenyl)-methyl]-3-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-urea, [Ind_CC-074] N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-pyridine-2-carboxylic acid amide, [Ind_CC-075] 2-(2-chlorophenyl)-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro-[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-phenyl-acetamide, [Ind_CC-076] N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide, [Ind_CC-077] 2-(2-chlorophenyl)-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, [Ind_CC-078] 2,4-dichloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-079] 5-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-080] 3-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-081] N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide, [Ind_CC-082] 2-(2-chlorophenyl)-2-phenyl-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide, [Ind_CC-083] (E)-3-(2-chlorophenyl)-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acrylamide, [Ind_CC-084] N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic acid amide, [Ind_CC-085] 1-(3,4-dichlorophenyl)-3-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, [Ind_CC-086] 1-[(2-chlorophenyl)-methyl]-3-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea, [Ind_CC-087] 4-methoxy-2,6-dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [Ind_CC-088] 4-methoxy-2,6-dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-089] 2-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide, [Ind_CC-090] 4-methoxy-2,6-dimethyl-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-091] N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethyl-benzamide, [Ind_CC-092] 4-methoxy-2,6-dimethyl-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-093] N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethyl-benzamide, [Ind_CC-094] 4-methoxy-2,6-dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-095] 2-chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-096] 2-chloro-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-097] 2-chloro-N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-098] 2-chloro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-099] 2-chloro-N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-100] 2-chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-101] 2-chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-102] 3-chloro-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-103] 3-chloro-N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-104] 3-chloro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-105] 3-chloro-N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide, [Ind_CC-106] 2-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-107] 2-chloro-N-methyl-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-108] 2-chloro-N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide, [Ind_CC-109] 2-chloro-N-methyl-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-110] 2-chloro-N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide, [Ind_CC-111] 2-chloro-N-methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-112] 2-chloro-N-methyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-113] 2-chloro-N-cyclopropyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-114] 2-chloro-N-cyclopropyl-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-115] 2-chloro-N-cyclopropyl-N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-116] 2-chloro-N-cyclopropyl-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-117] 2-chloro-N-cyclopropyl-N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-118] 2-chloro-N-cyclopropyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-119] 2-chloro-N-cyclopropyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-120] 2-chloro-N-[3-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide, [Ind_CC-121] 2-chloro-N-[3-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide, [Ind_CC-122] 2-chloro-N-[3-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide, [Ind_CC-123] 2-chloro-N-[3-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide [Ind_CC-124] 2-chloro-N-[3-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide, [Ind_CC-125] 2-chloro-N-[3-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide, [Ind_CC-126] 2-chloro-N-[3-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide, [Ind_CC-127] 2-chloro-N-[[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, [Ind_CC-128] 2-chloro-N-[[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, [Ind_CC-129] 2-chloro-N-[[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, [Ind_CC-130] 2-chloro-N-[[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, [Ind_CC-131] 2-chloro-N-[[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, [Ind_CC-132] 2-chloro-N-[[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, [Ind_CC-133] 2-chloro-N-[[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide, [Ind_CC-134] 2-chloro-N-[6-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-yl)-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-135] 2-chloro-N-[6-[2-oxo-2-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-yl)-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-136] 2-chloro-N-[6-[2-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-yl]-2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-137] 2-chloro-N-[6-[2-oxo-2-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-yl]-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-138] 2-chloro-N-[6-[2-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]-undecane-3-yl]-2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-139] 2-chloro-N-[6-[2-oxo-2-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-yl)-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-140] 2-chloro-N-[6-[2-oxo-2-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-yl)-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide, [Ind_CC-141] 8-chloro-2-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, [Ind_CC-142] 8-chloro-2-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, [Ind_CC-143] 8-chloro-2-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, [Ind_CC-144] 8-chloro-2-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, [Ind_CC-145] 8-chloro-2-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, [Ind_CC-146] 8-chloro-2-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, [Ind_CC-147] 8-chloro-2-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one, [Ind_CC-148] 8-chloro-4-methyl-2-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one, [Ind_CC-149] 8-chloro-4-methyl-2-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one, [Ind_CC-150] 8-chloro-2-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methyl-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one, [Ind_CC-151] 8-chloro-4-methyl-2-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one, [Ind_CC-152] 8-chloro-2-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methyl-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one, [Ind_CC-153] 8-chloro-4-methyl-2-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one and [Ind_CC-154] 8-chloro-4-methyl-2-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one. [IND_CC-200] 2,5-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-201] 2-Chloro-4-methoxy-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-202] 2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-203]2-Chloro-5-fluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-204]2-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide [IND_CC-205] 2-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide [IND_CC-206] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-6-(trifluoromethyl)-benzamide [IND_CC-207] 2,5-Dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-208] 2,5-Dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-209] 2,5-Dichloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-210] 2,5-Dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide [IND_CC-211] 2-Chloro-4-methoxy-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-212] 2-Chloro-4-methoxy-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-213] 2-Chloro-4-methoxy-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-214] 2-Chloro-6-fluoro-3-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-215] 2-Chloro-6-fluoro-3-methyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-216] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-6-fluoro-3-methyl-benzamide [IND_CC-217] 2-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-218] 2-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-219] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-220] 2-Chloro-5-fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-221] 2-Chloro-5-fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-222] 2-Chloro-5-fluoro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-223] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-5-fluoro-benzamide [IND_CC-224] 2-Chloro-4,5-difluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-225] 2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzamide [IND_CC-226] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic acid amide [IND_CC-227] 2-Chloro-N,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-228] 2-Chloro-4,5-difluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-229] 2-Chloro-4,5-difluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-230] 2-Chloro-4,5-difluoro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-231] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4,5-difluoro-benzamide [IND_CC-232] 2-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzamide [IND_CC-233] 2-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzamide [IND_CC-234] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-3-(trifluoromethyl)-benzamide [IND_CC-235] 2-Cyano-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-236] N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic acid amide [IND_CC-237] N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic acid amide [IND_CC-238] N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic acid amide [IND_CC-239] 2-Chloro-6-methyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-240] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-6-methyl-benzenesulfonic acid amide [IND_CC-241] 2-(2-Chlorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-ethanesulfonic acid amide [IND_CC-242] 2-(2-Chlorophenyl)-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-ethanesulfonic acid amide [IND_CC-243] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-6-(trifluoromethyl)-benzamide [IND_CC-244] 2,5-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide [IND_CC-245] 2,5-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-246] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-4-methoxy-benzamide [IND_CC-247] 2-Chloro-4-methoxy-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-248] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-6-fluoro-3-methyl-benzamide [IND_CC-249] 2-Chloro-6-fluoro-3-methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-250] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-251] 2-Chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-252] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-5-fluoro-benzamide [IND_CC-253] 2-Chloro-5-fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-254] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-3-(trifluoromethyl)-benzamide [IND_CC-255] 2-Chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzamide [IND_CC-256] N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic acid amide [IND_CC-258] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic acid amide [IND_CC-259] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-6-methyl-benzenesulfonic acid amide [IND_CC-260] 2-(2-Chlorophenyl)-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-ethanesulfonic acid amide [IND_CC-261] 2-Chloro-4-fluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-262] 2-Chloro-4-fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-263] 2-Chloro-4-fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-264] 2-Chloro-6-fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-265] 2,3-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-266] 2,3-Dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-267] 2,3-Dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-268] 2,6-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-269] 2,6-Dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-270] 2,6-Dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-271] 2-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-272] 2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-273] 2-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-274] 2-Chloro-4-fluoro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-275] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-fluoro-benzamide [IND_CC-276] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-4-fluoro-benzamide [IND_CC-277] 2-Chloro-4-fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-278] 2-Chloro-6-fluoro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-279] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-6-fluoro-benzamide [IND_CC-280] 2-Chloro-6-fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-281] 2,3-Dichloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-282] 2,3-Dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide [IND_CC-283] 2,3-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide [IND_CC-284] 2,3-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-286] 2,6-Dichloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-287] 2,6-Dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide [IND_CC-288] 2,6-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide [IND_CC-289] 2,6-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-290] 2-Chloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-291] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide [IND_CC-292] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide [IND_CC-293] 2-Chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-294] 2,6-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-295] 2,6-Dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-296] 2-Fluoro-4-methoxy-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-297] 2-Fluoro-4-methoxy-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-298] 2-Fluoro-4-methoxy-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-299]N,2-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyloxy)-benzamide [IND_CC-300] 2-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyloxy)-benzamide [IND_CC-301] 5-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide [IND_CC-302] 5-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide [IND_CC-303] 5-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide [IND_CC-304] 2-Fluoro-N,4-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-305] 2-Fluoro-4-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-306] 2-Fluoro-4-methyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-307] 2,6-Dimethyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-308] N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2,6-dimethyl-benzamide [IND_CC-309] N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-2,6-dimethyl-benzamide [IND_CC-310] 2,6-Dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-311] N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-fluoro-4-methoxy-benzamide [IND_CC-312] N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-2-fluoro-4-methoxy-benzamide [IND_CC-313] 2-Fluoro-4-methoxy-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-314] 5-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-(trifluoromethyl)-benzamide [IND_CC-315] 5-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-2-(trifluoromethyl)-benzamide [IND_CC-316] 5-Chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide [IND_CC-317] N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-fluoro-4-methyl-benzamide [IND_CC-318] N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-2-fluoro-4-methyl-benzamide [IND_CC-319] 2-Fluoro-4-methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-320] 2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic acid amide [IND_CC-321] 2,6-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-322] 2,6-Dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-323] 2,6-Dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-324] 2,4-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-325] 2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-326] 4-Fluoro-N,2-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-327] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic acid amide [IND_CC-328] N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic acid amide [IND_CC-329] N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic acid amide [IND_CC-330] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic acid amide [IND_CC-331] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic acid amide [IND_CC-332] 2,6-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzenesulfonic acid amide [IND_CC-333] 2,6-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-334] 2,4-Dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzenesulfonic acid amide [IND_CC-335] 2,4-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzenesulfonic acid amide [IND_CC-336] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzenesulfonic acid amide [IND_CC-337] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzenesulfonic acid amide [IND_CC-338] N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-fluoro-2-methyl-benzenesulfonic acid amide [IND_CC-339] N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-4-fluoro-2-methyl-benzenesulfonic acid amide [IND_CC-340] N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic acid amide [IND_CC-341] N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic acid amide [IND_CC-342] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic acid amide [IND_CC-343] 2,3-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-344] 2,5-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-345]N,2-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-346] 2-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-347] 2-Methyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-348] 1-(2-Fluorophenyl)-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide [IND_CC-349] 1-(2-Fluorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide [IND_CC-350] 1-(2-Fluorophenyl)-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide [IND_CC-351] 1-(3-Chlorophenyl)-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide [IND_CC-352] 1-(3-Chlorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide [IND_CC-353] 1-(3-Chlorophenyl)-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide [IND_CC-354] 4-Fluoro-N,2,6-trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-355] 4-Fluoro-2,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-356] 4-Fluoro-2,6-dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-357] 2,5-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-358] 2-Methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-359] 1-(2-Fluorophenyl)-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide [IND_CC-360] 1-(3-Chlorophenyl)-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide [IND_CC-361] 4-Fluoro-2,6-dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-362] 2,4,5-Trichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-363] 2,4,5-Trichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-364] N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclohexanecarboxylic acid amide [IND_CC-365] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclohexanecarboxylic acid amide [IND_CC-366] N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclohexanecarboxylic acid amide [IND_CC-367] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclohexanecarboxylic acid amide [IND_CC-368] N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopropanecarboxylic acid amide [IND_CC-369] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopropanecarboxylic acid amide [IND_CC-370] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopropanecarboxylic acid amide [IND_CC-371] 3,3-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide [IND_CC-372]N,3,3-Trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide [IND_CC-373] 3,3-Dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide [IND_CC-374] 3,3-Dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide [IND_CC-375] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide [IND_CC-376] 2-Fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide [IND_CC-377] 2-Fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide [IND_CC-378] 2-Fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide [IND_CC-379] 4-Fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide [IND_CC-380] 4-Fluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide [IND_CC-381] 4-Fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide [IND_CC-382] 4-Fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide [IND_CC-383] 2,6-Difluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-384] 2,6-Difluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-385] 2,6-Difluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-386] 2,6-Difluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-387]N,2,3-Trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-388] 2,3-Dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-389] 2,3-Dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-390] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[3-(trifluoromethyl)phenyl]-methanesulfonic acid amide [IND_CC-391] N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopentanecarboxylic acid amide [IND_CC-392] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopentanecarboxylic acid amide [IND_CC-393] N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopentanecarboxylic acid amide [IND_CC-394] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopentanecarboxylic acid amide [IND_CC-395] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-pyridine-2-carboxylic acid amide [IND_CC-396] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-pyridine-2-carboxylic acid amide [IND_CC-397] N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyrazine-2-carboxylic acid amide [IND_CC-398] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyrazine-2-carboxylic acid amide [IND_CC-399] 2-Fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-400] 2-Fluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-401] 2-Fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-402] 2-Fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-403] 2,6-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic acid amide [IND_CC-404] 2,6-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic acid amide [IND_CC-405] 4-Bromo-2-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-406] 2,4,6-Trichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-407] 2,4,6-Trichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide [IND_CC-408]N,3-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide [IND_CC-409] 3-Methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide [IND_CC-410] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide [IND_CC-411] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide [IND_CC-412] 3-Cyclopentyl-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide [IND_CC-413] 3-Cyclopentyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide [IND_CC-414] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclobutanecarboxylic acid amide [IND_CC-415] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclobutanecarboxylic acid amide [IND_CC-416]N,2-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide [IND_CC-417] 2-Methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide [IND_CC-418]N,2-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide [IND_CC-419] 2-Methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide [IND_CC-420] 2-Ethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide [IND_CC-500] 2-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-501] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-502] 2-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-chloro-4-fluoro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide [IND_CC-503] 2-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-cyano-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide [IND_CC-504] 2-Chloro-N-[6-[8-[(2,6-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-505] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide [IND_CC-506] 2-Chloro-N-methyl-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-507] 2-Chloro-N-[6-[9-(1H-pyrrol-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-508] 2-Chloro-N-[6-[9-(1H-imidazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-509] 2-Chloro-N-[6-[9-(pyridin-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-510] 2-Chloro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-511] 2-Chloro-N-[6-[9-(pyridin-3-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-512] 2-Chloro-N-[6-[9-[(1-methyl-1H-pyrrol-2-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-513] 2-Chloro-N-[6-[9-[(2,6-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-514] 2-Chloro-N-[6-[9-[(3,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-515] 2-Chloro-N-[6-[9-[(2,5-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-516] 2-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-517] 2-Chloro-N-[6-[9-[(2-fluoro-6-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-518] 2-Chloro-N-cyclopropyl-N-[6-[8-(pyridin-3-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-519] 2-Chloro-N-cyclopropyl-N-[6-[8-[(1-methyl-1H-pyrrol-2-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-520] 2-Chloro-N-cyclopropyl-N-[6-[8-[(2,6-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-521] 2-Chloro-N-cyclopropyl-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-522] 2-Chloro-N-cyclopropyl-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-523] 2-Chloro-N-cyclopropyl-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-524] 2-Chloro-N-cyclopropyl-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-525] 2-Chloro-N-cyclopropyl-N-[6-[8-[(2-fluoro-6-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-526] 2-Chloro-N-[6-[9-[(3-methyl-3H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-527] 2-Chloro-N-[6-[9-[(5-methyl-3H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-528] 2-Chloro-N-[6-[9-[(2-methyl-1H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-529] 2-Chloro-N-[6-[9-[(2-chloro-4-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-530] 2-Chloro-N-[6-[9-[(2-chloro-6-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-531] 2-Chloro-N-[6-[9-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-532] 2-Chloro-N-[6-[9-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-533] 2-Chloro-N-[6-[9-[(4-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-534] 2-Chloro-N-[6-[9-[(3-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-535] 2-Chloro-N-[6-[9-[(2-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-536] 2-Chloro-N-cyclopropyl-N-[6-[8-[(3-methyl-3H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-537] 2-Chloro-N-[6-[8-[(2-chloro-4-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide [IND_CC-538] 2-Chloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide [IND_CC-539] 2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide [IND_CC-540] 2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide [IND_CC-541] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide [IND_CC-542] 2-Chloro-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-543] 2-Chloro-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-544] 2-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-545] 2-Chloro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-546] 2-Chloro-N-[6-[8-[(2-fluoro-6-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-547] 3-Chloro-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide [IND_CC-548] 3-Chloro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide [IND_CC-549] 2-Chloro-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide [IND_CC-550] 2-Chloro-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide [IND_CC-551] 2-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide [IND_CC-552] 2-Chloro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide [IND_CC-553] 2-Chloro-N-[6-[8-[(5-methyl-3H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-554] 2-Chloro-N-[6-[8-[(2-methyl-1H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-555] 2-Chloro-N-[6-[8-([1,2,3]thiadiazol-4-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-556] 2-Chloro-N-[6-[8-[(2-chloro-4-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-557] 2-Chloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-558] 2-Chloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide [IND_CC-559] 2-Chloro-N-[6-[8-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-560] 2-Chloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-561] 2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-562] 2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-563] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-564] 2-Chloro-N-[6-[8-[(1,3,5-trimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-565] 2-Chloro-N-[6-[8-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-566] 2-Chloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-567] 2-Chloro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-568] 2-Chloro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-569] 3-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide [IND_CC-570] 3-Chloro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide [IND_CC-571] 3-Chloro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide [IND_CC-572] 2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide [IND_CC-573] 2-Chloro-N-[6-[8-(cyclopropanecarbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-574] 2-Chloro-N-[6-[8-(3,3-dimethyl-butanoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-575] 2-Chloro-N-[6-[8-(2-chloro-4-fluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-576] 2-Chloro-N-[6-[8-(2,4-difluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-577] 2-Chloro-N-[6-[8-[2-(4-chlorophenyl)-acetyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-578] N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chlorobenzamide [IND_CC-579] N-[6-[8-(2-tert-Butyl-5-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chlorobenzamide [IND_CC-580] N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethylbenzamide [IND_CC-581] N-[6-[8-(2-tert-Butyl-5-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethylbenzamide [IND_CC-582] 3-Chloro-N-[6-[8-(cyclopropanecarbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide [IND_CC-583] 3-Chloro-N-[6-[8-(3,3-dimethyl-butanoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide [IND_CC-584] 3-Chloro-N-[6-[8-(2-chloro-4-fluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide [IND_CC-585] 3-Chloro-N-[6-[8-(2,4-difluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide [IND_CC-586] 3-Chloro-N-[6-[8-[2-(4-chlorophenyl)-acetyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide [IND_CC-587] N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3-chloro-thiophene-2-carboxylic acid amide [IND_CC-588] N-[6-[8-(2-tert-Butyl-5-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3-chloro-thiophene-2-carboxylic acid amide [IND_CC-589] 2-Chloro-N-[6-[8-(cyclopropanecarbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide [IND_CC-590] 2-Chloro-N-[6-[8-(3,3-dimethyl-butanoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide [IND_CC-591] 2-Chloro-N-[6-[8-(2-chloro-4-fluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide [IND_CC-592] 2-Chloro-N-[6-[8-[2-(4-chlorophenyl)-acetyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide [IND_CC-593] N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-N-methylbenzamide [IND_CC-594] 2-Chloro-N-[6-[9-(pyrazine-2-carbonyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-595] 2-Chloro-N-[6-[9-(2-methylsulfanyl-pyridine-3-carbonyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-596] 2-Chloro-N-[6-[9-(4-cyano-benzoyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-597] 2-Chloro-N-[6-[9-(cyclopropanecarbonyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-598] 2-Chloro-N-[6-[9-(3,3-dimethyl-butanoyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-599] 2-Chloro-N-[6-[9-(2-chloro-4-fluoro-benzoyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-600] 2-Chloro-N-[6-[9-(2,4-difluoro-benzoyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-601] N-[6-[9-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide [IND_CC-602] N-[6-[9-(2-tert-Butyl-5-methyl-2H-pyrazole-3-carbonyl)-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide [IND_CC-603] 2-Chloro-N-[6-[8-(cyclopropanecarbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide [IND_CC-604] 2-Chloro-N-cyclopropyl-N-[6-[8-(3,3-dimethyl-butanoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-605] 2-Chloro-N-[6-[8-(2-chloro-4-fluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide [IND_CC-606] 2-Chloro-N-cyclopropyl-N-[6-[8-(2,4-difluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-607] N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-N-cyclopropylbenzamide [IND_CC-608] 2-Chloro-N-[6-[9-[(5-chloro-thiophen-2-yl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-609] 2-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-610] 2-Chloro-N-[6-[9-[(3-cyano-4-fluoro-phenyl)sulfonyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-611] 2-Chloro-N-[6-[9-[(2-cyano-phenyl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-612] 2-Chloro-N-[6-[9-[(1-methyl-1H-indol-4-yl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-613] 2-Chloro-N-[6-[9-(isopropylsulfonyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-614] 2-Chloro-N-[6-[9-[(1-methyl-1H-indol-5-yl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-615] 2-Chloro-N-[6-[8-[(5-chloro-thiophen-2-yl)sulfonyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide [IND_CC-616] 2-Chloro-N-cyclopropyl-N-[6-[8-[(2,4-difluoro-phenyl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-617] 2-Chloro-N-[6-[8-[(3-cyano-4-fluoro-phenyl)sulfonyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide [IND_CC-618] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide [IND_CC-619] 2-Chloro-N-cyclopropyl-N-[6-[8-[(1-methyl-1H-indol-5-yl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-620] 5-Chloro-2-fluoro-N-[6-[8-(1H-pyrrol-2-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-621] 5-Chloro-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide [IND_CC-622] 5-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide [IND_CC-623] 5-Chloro-2-fluoro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-624] 5-Chloro-2-fluoro-N-[6-[9-(1H-pyrrol-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-625] 5-Chloro-2-fluoro-N-[6-[9-(1H-imidazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-626] 5-Chloro-2-fluoro-N-[6-[9-(pyridin-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-627] 5-Chloro-2-fluoro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-628] 5-Chloro-N-[6-[9-[(3,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide [IND_CC-629] 5-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide [IND_CC-630] 5-Chloro-2-fluoro-N-[6-[9-[(3-fluoro-4-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-631] 2-Chloro-N-[6-[8-(1H-imidazol-4-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-632] 2-Chloro-N-[6-[8-[(2,6-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-633] 2-Chloro-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-634] 2-Chloro-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-635] 2-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-636] 2-Chloro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-637] 2-Chloro-N-[6-[8-[(2-fluoro-6-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-638] 2-Chloro-N-[6-[9-(1H-pyrrol-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-639] 2-Chloro-N-[6-[9-(1H-imidazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-640] 2-Chloro-N-[6-[9-(pyridin-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-641] 2-Chloro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-642] 2-Chloro-N-[6-[9-(pyridin-3-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-643] 2-Chloro-N-[6-[9-[(1-methyl-1H-pyrrol-2-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-644] 2-Chloro-N-[6-[9-[(2,6-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-645] 2-Chloro-N-[6-[9-[(3,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-646] 2-Chloro-N-[6-[9-[(2,5-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-647] 2-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-648] 2-Chloro-N-[6-[9-[(3-fluoro-4-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide [IND_CC-649] 2-Chloro-N-[6-[9-[(2-fluoro-6-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide [IND_CC-650] 5-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide [IND_CC-651] 5-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide [IND_CC-652] 5-Chloro-2-fluoro-N-[6-[9-([1,2,3]thiadiazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-653] 5-Chloro-N-[6-[9-[(4-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide [IND_CC-654] 5-Chloro-N-[6-[9-[(3-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide [IND_CC-655] 2-Chloro-N-[6-[8-[(5-methyl-3H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-656] 2-Chloro-N-[6-[8-([1,2,3]thiadiazol-4-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-657] 2-Chloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-658] 2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-659] 2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-660] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-661] 2-Chloro-N-[6-[9-[(5-methyl-3H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide [IND_CC-662] 2-Chloro-N-[6-[9-[(2-methyl-1H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide [IND_CC-663] 2-Chloro-N-[6-[9-([1,2,3]thiadiazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-664] 2-Chloro-N-[6-[9-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide [IND_CC-665] 2-Chloro-N-[6-[9-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide [IND_CC-666] 2-Chloro-N-[6-[9-[(4-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-667] 2-Chloro-N-[6-[9-[(3-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-668] 2-Chloro-N-[6-[9-[(2-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-669] 2-Chloro-N-[6-[9-[(2-chloro-4-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide [IND_CC-670] 2-Chloro-N-[6-[9-[(2-chloro-6-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide [IND_CC-671] 5-Chloro-2-fluoro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-672] 5-Chloro-2-fluoro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-673] 5-Chloro-2-fluoro-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-674] 5-Chloro-2-fluoro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-675] 5-Chloro-2-fluoro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-676] 5-Chloro-N-[6-[9-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide [IND_CC-677] 5-Chloro-2-fluoro-N-[6-[9-(quinolin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-678] 5-Chloro-2-fluoro-N-[6-[9-(quinoxalin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-679] 5-Chloro-2-fluoro-N-[6-[9-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-680] 5-Chloro-2-fluoro-N-[6-[9-(2-methyl-propyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-681] 5-Chloro-2-fluoro-N-[6-(9-phenethyl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-682] 2-Chloro-5-(trifluoromethyl)-N-[6-[8-[(1,3,5-trimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-683] 2-Chloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-684] 2-Chloro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-685] 2-Chloro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-686] 2-Chloro-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide [IND_CC-687] 2-Chloro-N-[6-[8-(2-methyl-propyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-688] 2-Chloro-N-[6-[8-(2-ethyl-butyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-689] 2-Chloro-N-[6-[8-(cyclohexyl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-690] 2-Chloro-N-[6-(8-phenethyl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-691] 2-Chloro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-692] 2-Chloro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-693] 2-Chloro-N-[6-[9-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-694] 2-Chloro-N-[6-[9-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide [IND_CC-695] 2-Chloro-N-[6-[9-(quinolin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-696] 2-Chloro-N-[6-[9-(quinoxalin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-697] 2-Chloro-N-[6-[9-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide [IND_CC-698] 2-Chloro-N-[6-[9-(2-methyl-propyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-699] 2-Chloro-N-[6-[9-(2-ethyl-butyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-700] 2-Chloro-N-[6-[9-(cyclohexyl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-701] 2-Chloro-N-[6-(9-phenethyl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-702] 2-Chloro-N-[6-[9-[3-(3-fluorophenyl)-propyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-703] 2-Chloro-N-[6-[9-[3-(4-fluorophenyl)-propyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide [IND_CC-704] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-propyl-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide [IND_CC-705] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-cyano-phenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide [IND_CC-706] N-Benzyl-3-[3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide [IND_CC-707] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(4-dimethylaminophenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide [IND_CC-708] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-cyclohexyl-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide [IND_CC-709] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,6-dichloro-phenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide [IND_CC-710] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,4-dichlorophenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide [IND_CC-711] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,4-difluoro-phenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide [IND_CC-712] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-propyl-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide [IND_CC-713] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-chloro-4-fluoro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide [IND_CC-714] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-[4-chloro-2-(trifluoromethyl)-phenyl]-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide [IND_CC-715] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-cyano-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide [IND_CC-716] N-Benzyl-2-[3-[(2-chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide [IND_CC-717] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-cyclohexyl-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide [IND_CC-718] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,6-dichloro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide [IND_CC-719] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,4-difluoro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide [IND_CC-720] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3,5-difluoro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide [IND_CC-721] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-[(3,4-dichlorophenyl)-methyl]-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide [IND_CC-722] 2,3-Dichloro-N-[6-[8-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-723] 2,3-Dichloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-724] 2,3-Dichloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-725] 2,3-Dichloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-726] 2,3-Dichloro-N-[6-[9-[(2-chloro-4-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-727] 2,3-Dichloro-N-[6-[9-[(2-chloro-6-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-728] 2-Chloro-6-methyl-N-[6-[8-[(2-methyl-1H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-729] 2-Chloro-N-[6-[8-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide [IND_CC-730] 2-Chloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide [IND_CC-731] 2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide [IND_CC-732] 2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide [IND_CC-733] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide [IND_CC-734] 2-Chloro-N-[6-[8-[(2-chloro-4-fluoro-phenyl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide [IND_CC-735] 2-Chloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide [IND_CC-736] 2-Chloro-6-fluoro-N-[6-[8-[(2-methyl-1H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-737] 2-Chloro-N-[6-[8-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-738] 2-Chloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-739] 2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-740] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-741] 2-Chloro-N-[6-[8-[(2-chloro-4-fluoro-phenyl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-742] 2,3-Dichloro-N-[6-[8-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-743] 2,3-Dichloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-744] 2,3-Dichloro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-745] 2,3-Dichloro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-746] 2,3-Dichloro-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-747] 2,3-Dichloro-N-[6-[8-(2-methyl-propyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-748] 2,3-Dichloro-N-[6-[8-(2-ethyl-butyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-749] 2,3-Dichloro-N-[6-(8-phenethyl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-750] 2,3-Dichloro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-751] 2,3-Dichloro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-752] 2,3-Dichloro-N-[6-[9-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-753] 2,3-Dichloro-N-[6-[9-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-754] 2,3-Dichloro-N-[6-[9-(quinolin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-755] 2,3-Dichloro-N-[6-[9-(quinoxalin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-756] 2,3-Dichloro-N-[6-[9-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-757] 2,3-Dichloro-N-[6-[9-(2-methyl-propyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-758] 2,3-Dichloro-N-[6-(9-phenethyl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-759] 2,3-Dichloro-N-[6-[9-[3-(3-fluorophenyl)-propyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-760] 2,3-Dichloro-N-[6-[9-[3-(4-fluorophenyl)-propyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-761] 2-Chloro-6-methyl-N-[6-[8-[(1,3,5-trimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-762] 2-Chloro-N-[6-[8-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide [IND_CC-763] 2-Chloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide [IND_CC-764] 2-Chloro-6-methyl-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-765] 2-Chloro-6-methyl-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-766] 2-Chloro-6-methyl-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-767] 2-Chloro-6-methyl-N-[6-[8-(2-methyl-propyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-768] 2-Chloro-N-[6-[8-(2-ethyl-butyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide [IND_CC-769] 2-Chloro-6-methyl-N-[6-(8-phenethyl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-770] 2-Chloro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide [IND_CC-771] 2-Chloro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide [IND_CC-772] 2-Chloro-N-[6-[8-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-773] 2-Chloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-774] 2-Chloro-6-fluoro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-775] 2-Chloro-6-fluoro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-776] 2-Chloro-6-fluoro-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-777] 2-Chloro-6-fluoro-N-[6-[8-(2-methyl-propyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-778] 2-Chloro-N-[6-[8-(2-ethyl-butyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-779] 2-Chloro-N-[6-[8-(cyclohexyl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-780] 2-Chloro-6-fluoro-N-[6-(8-phenethyl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-781] 2-Chloro-6-fluoro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-782] 2-Chloro-6-fluoro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-783] 2-Chloro-6-fluoro-N-[6-[9-(1H-pyrrol-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-784] 2-Chloro-6-fluoro-N-[6-[9-(pyridin-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-785] 2-Chloro-6-fluoro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-786] 2-Chloro-6-fluoro-N-[6-[9-(pyridin-3-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-787] 2-Chloro-6-fluoro-N-[6-[9-[(1-methyl-1H-pyrrol-2-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-788] 2-Chloro-N-[6-[9-[(2,6-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-789] 2-Chloro-N-[6-[9-[(3,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-790] 2-Chloro-N-[6-[9-[(2,5-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-791] 2-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-792] 2-Chloro-6-fluoro-N-[6-[9-[(3-fluoro-4-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-793] 2-Chloro-6-fluoro-N-[6-[9-[(2-fluoro-6-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-794] 8-Chloro-2-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methyl-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one [IND_CC-795] 8-Chloro-2-[6-[8-[(2-fluoro-6-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methyl-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one [IND_CC-796] 2-Chloro-6-fluoro-N-[6-[9-[(3-methyl-3H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-797] 2-Chloro-6-fluoro-N-[6-[9-([1,2,3]thiadiazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-798] 2-Chloro-N-[6-[9-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-799] 2-Chloro-N-[6-[9-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-800] 2-Chloro-N-[6-[9-[(3-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-801] 2-Chloro-N-[6-[9-[(2-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-802] 2-Chloro-N-[6-[9-[(2-chloro-4-fluoro-phenyl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-803] 2-Chloro-N-[6-[9-[(2-chloro-6-fluoro-phenyl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide [IND_CC-804] 2-Chloro-N-[6-[2-oxo-2-[8-(quinolin-6-yl-methyl)-3,8-diazaspiro[4.5]decan-3-yl]-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-805] 2-Chloro-N-[6-[2-oxo-2-[8-(quinoxalin-6-yl-methyl)-3,8-diazaspiro[4.5]decan-3-yl]-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-806] 2-Chloro-N-[6-[2-[8-(2-ethyl-butyl)-3,8-diazaspiro[4.5]decan-3-yl]-2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide [IND_CC-807] 2-Chloro-N-[6-[2-[8-(cyclohexyl-methyl)-3,8-diazaspiro[4.5]decan-3-yl]-2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide and physiologically acceptable salts of any of the foregoing.
 18. A pharmaceutical composition comprising a compound as claimed in claim 1 and at least one pharmaceutically acceptable carrier or auxiliary.
 19. A method of treating or inhibiting a condition selected from the group consisting of pain migraine; diabetes; respiratory tract diseases; inflammatory intestinal diseases; neurological diseases; neurodegenerative diseases, fibrotic diseases, skin inflammations; rheumatic diseases; septic shock; reperfusion syndrome, and obesity, or of inhibiting angiogenesis, said method comprising administering to a subject in need thereof, a pharmaceutically effective amount of a compound as claimed in claim
 1. 20. A method as claimed in claim 19, wherein said condition is pain selected from the group consisting of acute pain, visceral pain, neuropathic pain, chronic pain and inflammation pain. 